Sharing MAVE functional evidence as computable statements with VA-Spec¶
Why this matters
Multiplexed assays measure how genetic variants behave in the lab, and those measurements are some of the strongest evidence available for deciding whether a variant is pathogenic. But that evidence has historically lived as spreadsheets of numbers that a human had to find, interpret, and transcribe before it could inform a clinical assessment. MaveDB now publishes each measurement as a structured statement that records the score, what was measured, how, by whom, and where it came from — in a shared format that variant-interpretation systems can read automatically. Experimental evidence becomes something software can pick up and use, with its full provenance attached.
At a glance
- Who: MaveDB
- GKS products used: VA-Spec 0.4, building on VRS 2.0 variants
- Tools: ga4gh-va-spec (
ga4gh-va-spec~0.4.2), MaveDB annotation pipeline - Status: production
The story¶
A multiplexed assay of variant effect produces a functional score for each variant — a number summarizing how the variant behaved in the experiment. On its own, a score is hard to reuse: a downstream consumer needs to know which variant it refers to (precisely), what the number means, how it was generated, and whether its provenance is trustworthy enough to act on.
MaveDB expresses this using the GA4GH Variant Annotation Specification (VA-Spec), as a stack of three statement types at rising altitudes.
At the base is the ExperimentalVariantFunctionalImpactStudyResult — the raw measurement. Its focusVariant is the variant's VRS allele, anchoring the evidence to a precise, content-addressed identity rather than a free-text label, and functionalImpactScore carries the measured value. Around that it records structured provenance: a contributions chain naming the MaveDB API and VRS-mapping software (with versions), the original submitter (by ORCID), and the relevant dates; a sourceDataSet describing the score set, its publication, and its license; and reportedIn links back to the live MaveDB records. MaveDB emits one for every mappable variant in every published score set.
Calibration is what turns a raw score into evidence: using reference variants of known effect, it sets the score thresholds — and the ACMG evidence strength (supporting, moderate, strong) — at which the assay's scores support a normal or abnormal functional call. Where a score set has been calibrated, MaveDB raises its raw results into a per-assay functional-impact Statement — the assay's normal/abnormal call. It aggregates the assay's calibrations into a single functional classification (for example abnormal or normal) rooted in the study result beneath it: the assay saying what its numbers mean, not just what they were.
At the top sits a variant-level pathogenicity Statement, the only layer that aggregates across assays. It carries one evidence line per assay that measured the variant — each wrapping that assay's functional-impact statement, scored against an ACMG criterion such as PS3 — and integrates them into an ACMG-style classification. Crucially, it integrates MaveDB's functional evidence only: it is the functional contribution to a classification, not a standalone clinical verdict, which also requires population, segregation, and computational evidence that a downstream knowledgebase supplies. The layers nest — a pathogenicity statement contains its functional statements, which contain their study results — so a single object can carry the conclusion together with the full evidentiary chain beneath it. Because the evidence is structured and VRS-anchored at every level, a variant-interpretation pipeline can ingest any of these layers directly.
The data¶
Two real exports, at opposite ends of the stack.
The base unit — an ExperimentalVariantFunctionalImpactStudyResult for UBE2I p.Leu6Gly (urn:mavedb:00000001-a-1#2323, from the Weile et al., 2017 score set). Its focusVariant.id is exactly the VRS digest produced by the variant-mapping pattern:
ExperimentalVariantFunctionalImpactStudyResult — UBE2I p.Leu6Gly
{
"type": "ExperimentalVariantFunctionalImpactStudyResult",
"description": "Variant effect study result for urn:mavedb:00000001-a-1#2323.",
"specifiedBy": {
"type": "Method",
"name": "Experimental protocol",
"reportedIn": "http://www.ncbi.nlm.nih.gov/pubmed/29269382"
},
"contributions": [
{
"type": "Contribution",
"name": "MaveDB API",
"description": "Contribution from the MaveDB API",
"contributor": {
"type": "Agent",
"name": "MaveDB API",
"description": "MaveDB API agent, version 2026.2.5",
"extensions": [
{
"name": "mavedbApiVersion",
"value": "2026.2.5"
}
],
"agentType": "Software"
},
"activityType": "software application programming interface",
"date": "2026-06-24 18:13:21.636210"
},
{
"type": "Contribution",
"name": "MaveDB VRS Mapper",
"description": "Contribution from the MaveDB VRS mapping software",
"contributor": {
"type": "Agent",
"name": "MaveDB VRS Mapping Agent",
"description": "MaveDB VRS mapping agent, version 2026.2.0",
"extensions": [
{
"name": "mavedbVrsVersion",
"value": "2026.2.0"
}
],
"agentType": "Software"
},
"activityType": "human genome sequence mapping process",
"date": "2026-06-10 00:00:00"
},
{
"type": "Contribution",
"name": "MaveDB Dataset Creator",
"description": "When this resource was first submitted, and by whom.",
"extensions": [
{
"name": "resourceType",
"value": "Variant"
}
],
"contributor": {
"type": "Agent",
"name": "0000-0003-1628-9390",
"description": "MaveDB ORCid authenticated user 0000-0003-1628-9390",
"agentType": "Person"
},
"activityType": "http://purl.obolibrary.org/obo/CRO_0000105",
"date": "2018-06-26 00:00:00"
},
{
"type": "Contribution",
"name": "MaveDB Dataset Modifier",
"description": "When this resource was last modified, and by whom.",
"extensions": [
{
"name": "resourceType",
"value": "Variant"
}
],
"contributor": {
"type": "Agent",
"name": "0000-0003-1628-9390",
"description": "MaveDB ORCid authenticated user 0000-0003-1628-9390",
"agentType": "Person"
},
"activityType": "http://purl.obolibrary.org/obo/CRO_0000103",
"date": "2019-02-14 00:00:00"
}
],
"reportedIn": [
"https://mavedb.org/score-sets/urn:mavedb:00000001-a-1?variant=urn%3Amavedb%3A00000001-a-1%232323",
"https://mavedb.org/variant/PA2579755325"
],
"sourceDataSet": {
"id": "urn:mavedb:00000001-a-1",
"type": "DataSet",
"name": "UBE2I imputed & refined",
"description": "A joint Deep Mutational Scan of the human SUMO E2 conjugase UBE2I using functional complementation in yeast, combining DMS-BarSeq and DMS-TileSeq data, followed by machine-learning-based imputation and refinement.",
"reportedIn": "https://mavedb.org/score-sets/urn:mavedb:00000001-a-1",
"releaseDate": "2018-06-26",
"license": {
"name": "CC0 (Public domain)",
"primaryCoding": {
"system": "https://spdx.org/licenses/",
"systemVersion": "1.0",
"code": "CC0-1.0",
"iris": [
"https://creativecommons.org/publicdomain/zero/1.0/"
]
}
}
},
"focusVariant": {
"id": "ga4gh:VA.P39KFBT8kdyfg79JH7IBX-4JKXGrzCxb",
"type": "Allele",
"extensions": [
{
"name": "vrs_ref_allele_seq",
"value": "L"
}
],
"digest": "P39KFBT8kdyfg79JH7IBX-4JKXGrzCxb",
"expressions": [
{
"syntax": "hgvs.p",
"value": "NP_003336.1:p.Leu6Gly"
}
],
"location": {
"id": "ga4gh:SL.o4bho24Xqm_HS5mD8-HDjtmtLCZ5XLez",
"type": "SequenceLocation",
"digest": "o4bho24Xqm_HS5mD8-HDjtmtLCZ5XLez",
"sequenceReference": {
"type": "SequenceReference",
"refgetAccession": "SQ.hy5ErT-cGJovsPYIgzchb3BvYQ2MkKB3"
},
"start": 5,
"end": 6
},
"state": {
"type": "LiteralSequenceExpression",
"sequence": "G"
}
},
"functionalImpactScore": 0.616282520019444
}
The apex — the full, real variant-level pathogenicity Statement for a GCK variant (urn:mavedb:00000096-a-1#2446, from this score set). It is classified pathogenic and aggregates two assays' evidence lines, each an ACMG 2015 PS3 Criterion Met at moderate strength, each wrapping an abnormal functional-impact statement rooted in its own study result — the entire evidentiary stack in one object. Note the proposition's condition: MedGen C0012634, the generic "Disease" concept. MaveDB currently calibrates its functional scores against this single generic disease condition rather than any gene-specific disorder, so the classification expresses functional impact toward disease in general, not a specific clinical diagnosis:
Pathogenicity Statement — GCK variant (1,332 lines)
{
"type": "Statement",
"description": "Variant pathogenicity statement for urn:mavedb:00000096-a-1#2446.",
"specifiedBy": {
"type": "Method",
"name": "ACMG standards and guidelines for the interpretation of sequence variants",
"reportedIn": "https://www.acmg.net/docs/standards_guidelines_for_the_interpretation_of_sequence_variants.pdf"
},
"contributions": [
{
"type": "Contribution",
"name": "MaveDB API",
"description": "Contribution from the MaveDB API",
"contributor": {
"type": "Agent",
"name": "MaveDB API",
"description": "MaveDB API agent, version 2026.2.5",
"extensions": [
{
"name": "mavedbApiVersion",
"value": "2026.2.5"
}
],
"agentType": "Software"
},
"activityType": "software application programming interface",
"date": "2026-06-24 18:44:14.755971"
},
{
"type": "Contribution",
"name": "MaveDB VRS Mapper",
"description": "Contribution from the MaveDB VRS mapping software",
"contributor": {
"type": "Agent",
"name": "MaveDB VRS Mapping Agent",
"description": "MaveDB VRS mapping agent, version 2026.2.0",
"extensions": [
{
"name": "mavedbVrsVersion",
"value": "2026.2.0"
}
],
"agentType": "Software"
},
"activityType": "human genome sequence mapping process",
"date": "2026-05-28 00:00:00"
},
{
"id": "urn:mavedb:calibration-b18c5122-57a0-4d54-90a7-9297411219c2",
"type": "Contribution",
"name": "IGVF Coding Variant Focus Group -- Controls: All Variants",
"description": "Contribution from a score calibration.",
"contributor": {
"type": "Agent",
"name": "AnonymousUser",
"description": "MaveDB ORCid authenticated user AnonymousUser",
"agentType": "Person"
},
"activityType": "variant specific calibration",
"date": "2025-11-14 00:00:00"
}
],
"proposition": {
"type": "VariantPathogenicityProposition",
"description": "Variant pathogenicity proposition for urn:mavedb:00000096-a-1#2446.",
"subjectVariant": {
"id": "ga4gh:VA.uKdR7fpiG9_r42oyAC33xQyd24VUNW3I",
"type": "Allele",
"extensions": [
{
"name": "vrs_ref_allele_seq",
"value": "F"
}
],
"digest": "uKdR7fpiG9_r42oyAC33xQyd24VUNW3I",
"expressions": [
{
"syntax": "hgvs.p",
"value": "NP_000153.1:p.Phe269Gln"
}
],
"location": {
"id": "ga4gh:SL.mr0SP5seWdgAplFqdmHBAbdhfmPcalZq",
"type": "SequenceLocation",
"digest": "mr0SP5seWdgAplFqdmHBAbdhfmPcalZq",
"sequenceReference": {
"type": "SequenceReference",
"refgetAccession": "SQ._mgLuM2tl_ap4JfYxyyr96JzV_FxAqsk"
},
"start": 268,
"end": 269
},
"state": {
"type": "LiteralSequenceExpression",
"sequence": "Q"
}
},
"geneContextQualifier": {
"primaryCoding": {
"system": "https://www.genenames.org/",
"code": "GCK"
}
},
"predicate": "isCausalFor",
"objectCondition": {
"conceptType": "Disease",
"primaryCoding": {
"system": "https://www.ncbi.nlm.nih.gov/medgen/",
"code": "C0012634",
"iris": [
"http://identifiers.org/medgen/C0012634"
]
}
}
},
"direction": "supports",
"classification": {
"primaryCoding": {
"system": "ACMG Guidelines, 2015",
"code": "pathogenic"
}
},
"hasEvidenceLines": [
{
"type": "EvidenceLine",
"description": "Pathogenicity evidence line for urn:mavedb:00000096-a-1#2446.",
"extensions": [
{
"name": "Containing classification name",
"value": "Decreased activity",
"description": "The name of the classification which contains this variant."
}
],
"specifiedBy": {
"type": "Method",
"name": "Calibration method",
"methodType": "PS3",
"reportedIn": "Not Provided"
},
"contributions": [
{
"type": "Contribution",
"name": "MaveDB API",
"description": "Contribution from the MaveDB API",
"contributor": {
"type": "Agent",
"name": "MaveDB API",
"description": "MaveDB API agent, version 2026.2.5",
"extensions": [
{
"name": "mavedbApiVersion",
"value": "2026.2.5"
}
],
"agentType": "Software"
},
"activityType": "software application programming interface",
"date": "2026-06-24 18:44:14.755235"
},
{
"type": "Contribution",
"name": "MaveDB VRS Mapper",
"description": "Contribution from the MaveDB VRS mapping software",
"contributor": {
"type": "Agent",
"name": "MaveDB VRS Mapping Agent",
"description": "MaveDB VRS mapping agent, version 2026.2.0",
"extensions": [
{
"name": "mavedbVrsVersion",
"value": "2026.2.0"
}
],
"agentType": "Software"
},
"activityType": "human genome sequence mapping process",
"date": "2026-05-28 00:00:00"
},
{
"id": "urn:mavedb:calibration-b18c5122-57a0-4d54-90a7-9297411219c2",
"type": "Contribution",
"name": "IGVF Coding Variant Focus Group -- Controls: All Variants",
"description": "Contribution from a score calibration.",
"contributor": {
"type": "Agent",
"name": "AnonymousUser",
"description": "MaveDB ORCid authenticated user AnonymousUser",
"agentType": "Person"
},
"activityType": "variant specific calibration",
"date": "2025-11-14 00:00:00"
}
],
"reportedIn": [
{
"id": "urn:mavedb:calibration-b18c5122-57a0-4d54-90a7-9297411219c2",
"type": "Document",
"name": "MaveDB Score Calibration",
"extensions": [
{
"name": "Baseline score",
"value": 1.0,
"description": "No description for this baseline score provided."
},
{
"name": "Research use only",
"value": false,
"description": "Indicates whether this score calibration is intended for research use only."
},
{
"name": "Primary calibration",
"value": true,
"description": "Indicates whether this score calibration is the primary calibration for its associated score set."
},
{
"name": "Investigator provided",
"value": false,
"description": "Indicates whether this score calibration was provided by the investigator rather than generated by MaveDB."
},
{
"name": "Hyperactive",
"value": [
1.18,
null
],
"description": "No description for this functional classification provided."
},
{
"name": "(0.66,1.18)",
"value": [
0.66,
1.18
],
"description": "No description for this functional classification provided."
},
{
"name": "Decreased activity",
"value": [
null,
0.66
],
"description": "No description for this functional classification provided."
}
],
"documentType": "score calibration",
"title": "IGVF Coding Variant Focus Group -- Controls: All Variants",
"urls": [
"https://mavedb.org/score-sets/urn:mavedb:00000096-a-1/calibrations?calibration=urn%3Amavedb%3Acalibration-b18c5122-57a0-4d54-90a7-9297411219c2"
]
}
],
"targetProposition": {
"type": "VariantPathogenicityProposition",
"description": "Variant pathogenicity proposition for urn:mavedb:00000096-a-1#2446.",
"subjectVariant": {
"id": "ga4gh:VA.uKdR7fpiG9_r42oyAC33xQyd24VUNW3I",
"type": "Allele",
"extensions": [
{
"name": "vrs_ref_allele_seq",
"value": "F"
}
],
"digest": "uKdR7fpiG9_r42oyAC33xQyd24VUNW3I",
"expressions": [
{
"syntax": "hgvs.p",
"value": "NP_000153.1:p.Phe269Gln"
}
],
"location": {
"id": "ga4gh:SL.mr0SP5seWdgAplFqdmHBAbdhfmPcalZq",
"type": "SequenceLocation",
"digest": "mr0SP5seWdgAplFqdmHBAbdhfmPcalZq",
"sequenceReference": {
"type": "SequenceReference",
"refgetAccession": "SQ._mgLuM2tl_ap4JfYxyyr96JzV_FxAqsk"
},
"start": 268,
"end": 269
},
"state": {
"type": "LiteralSequenceExpression",
"sequence": "Q"
}
},
"geneContextQualifier": {
"primaryCoding": {
"system": "https://www.genenames.org/",
"code": "GCK"
}
},
"predicate": "isCausalFor",
"objectCondition": {
"conceptType": "Disease",
"primaryCoding": {
"system": "https://www.ncbi.nlm.nih.gov/medgen/",
"code": "C0012634",
"iris": [
"http://identifiers.org/medgen/C0012634"
]
}
}
},
"hasEvidenceItems": [
{
"type": "Statement",
"description": "Variant functional impact statement for urn:mavedb:00000096-a-1#2446.",
"specifiedBy": {
"type": "Method",
"name": "Variant interpretation guideline",
"reportedIn": "https://pubmed.ncbi.nlm.nih.gov/29785012/"
},
"contributions": [
{
"type": "Contribution",
"name": "MaveDB API",
"description": "Contribution from the MaveDB API",
"contributor": {
"type": "Agent",
"name": "MaveDB API",
"description": "MaveDB API agent, version 2026.2.5",
"extensions": [
{
"name": "mavedbApiVersion",
"value": "2026.2.5"
}
],
"agentType": "Software"
},
"activityType": "software application programming interface",
"date": "2026-06-24 18:44:14.754872"
},
{
"type": "Contribution",
"name": "MaveDB VRS Mapper",
"description": "Contribution from the MaveDB VRS mapping software",
"contributor": {
"type": "Agent",
"name": "MaveDB VRS Mapping Agent",
"description": "MaveDB VRS mapping agent, version 2026.2.0",
"extensions": [
{
"name": "mavedbVrsVersion",
"value": "2026.2.0"
}
],
"agentType": "Software"
},
"activityType": "human genome sequence mapping process",
"date": "2026-05-28 00:00:00"
},
{
"id": "urn:mavedb:calibration-b18c5122-57a0-4d54-90a7-9297411219c2",
"type": "Contribution",
"name": "IGVF Coding Variant Focus Group -- Controls: All Variants",
"description": "Contribution from a score calibration.",
"contributor": {
"type": "Agent",
"name": "AnonymousUser",
"description": "MaveDB ORCid authenticated user AnonymousUser",
"agentType": "Person"
},
"activityType": "variant specific calibration",
"date": "2025-11-14 00:00:00"
}
],
"proposition": {
"type": "ExperimentalVariantFunctionalImpactProposition",
"description": "Variant functional impact proposition for urn:mavedb:00000096-a-1#2446.",
"subjectVariant": {
"id": "ga4gh:VA.uKdR7fpiG9_r42oyAC33xQyd24VUNW3I",
"type": "Allele",
"extensions": [
{
"name": "vrs_ref_allele_seq",
"value": "F"
}
],
"digest": "uKdR7fpiG9_r42oyAC33xQyd24VUNW3I",
"expressions": [
{
"syntax": "hgvs.p",
"value": "NP_000153.1:p.Phe269Gln"
}
],
"location": {
"id": "ga4gh:SL.mr0SP5seWdgAplFqdmHBAbdhfmPcalZq",
"type": "SequenceLocation",
"digest": "mr0SP5seWdgAplFqdmHBAbdhfmPcalZq",
"sequenceReference": {
"type": "SequenceReference",
"refgetAccession": "SQ._mgLuM2tl_ap4JfYxyyr96JzV_FxAqsk"
},
"start": 268,
"end": 269
},
"state": {
"type": "LiteralSequenceExpression",
"sequence": "Q"
}
},
"predicate": "impactsFunctionOf",
"objectSequenceFeature": {
"primaryCoding": {
"system": "https://www.genenames.org/",
"code": "GCK"
}
},
"experimentalContextQualifier": {
"id": "urn:mavedb:00000096-a",
"type": "Document",
"name": "MaveDB Experiment",
"description": "Activity of GCK variants measured by functional complementation of an hxk1\u0394hxk2\u0394glk1\u0394 yeast strain.",
"documentType": "experiment",
"title": "GCK activity measured by complementation",
"urls": [
"https://mavedb.org/experiments/urn:mavedb:00000096-a"
]
}
},
"direction": "supports",
"classification": {
"primaryCoding": {
"system": "ga4gh-gks-term:experimental-var-func-impact-classification",
"code": "abnormal"
}
},
"hasEvidenceLines": [
{
"type": "EvidenceLine",
"description": "Functional evidence line for urn:mavedb:00000096-a-1#2446",
"extensions": [
{
"name": "Containing functional classification",
"value": "Decreased activity",
"description": "The functional classification which contains this variant."
}
],
"specifiedBy": {
"type": "Method",
"name": "Calibration method",
"reportedIn": "http://www.ncbi.nlm.nih.gov/pubmed/37101203"
},
"contributions": [
{
"type": "Contribution",
"name": "MaveDB API",
"description": "Contribution from the MaveDB API",
"contributor": {
"type": "Agent",
"name": "MaveDB API",
"description": "MaveDB API agent, version 2026.2.5",
"extensions": [
{
"name": "mavedbApiVersion",
"value": "2026.2.5"
}
],
"agentType": "Software"
},
"activityType": "software application programming interface",
"date": "2026-06-24 18:44:14.754491"
},
{
"type": "Contribution",
"name": "MaveDB VRS Mapper",
"description": "Contribution from the MaveDB VRS mapping software",
"contributor": {
"type": "Agent",
"name": "MaveDB VRS Mapping Agent",
"description": "MaveDB VRS mapping agent, version 2026.2.0",
"extensions": [
{
"name": "mavedbVrsVersion",
"value": "2026.2.0"
}
],
"agentType": "Software"
},
"activityType": "human genome sequence mapping process",
"date": "2026-05-28 00:00:00"
},
{
"id": "urn:mavedb:calibration-b18c5122-57a0-4d54-90a7-9297411219c2",
"type": "Contribution",
"name": "IGVF Coding Variant Focus Group -- Controls: All Variants",
"description": "Contribution from a score calibration.",
"contributor": {
"type": "Agent",
"name": "AnonymousUser",
"description": "MaveDB ORCid authenticated user AnonymousUser",
"agentType": "Person"
},
"activityType": "variant specific calibration",
"date": "2025-11-14 00:00:00"
}
],
"reportedIn": [
{
"id": "urn:mavedb:calibration-b18c5122-57a0-4d54-90a7-9297411219c2",
"type": "Document",
"name": "MaveDB Score Calibration",
"extensions": [
{
"name": "Baseline score",
"value": 1.0,
"description": "No description for this baseline score provided."
},
{
"name": "Research use only",
"value": false,
"description": "Indicates whether this score calibration is intended for research use only."
},
{
"name": "Primary calibration",
"value": true,
"description": "Indicates whether this score calibration is the primary calibration for its associated score set."
},
{
"name": "Investigator provided",
"value": false,
"description": "Indicates whether this score calibration was provided by the investigator rather than generated by MaveDB."
},
{
"name": "Hyperactive",
"value": [
1.18,
null
],
"description": "No description for this functional classification provided."
},
{
"name": "(0.66,1.18)",
"value": [
0.66,
1.18
],
"description": "No description for this functional classification provided."
},
{
"name": "Decreased activity",
"value": [
null,
0.66
],
"description": "No description for this functional classification provided."
}
],
"documentType": "score calibration",
"title": "IGVF Coding Variant Focus Group -- Controls: All Variants",
"urls": [
"https://mavedb.org/score-sets/urn:mavedb:00000096-a-1/calibrations?calibration=urn%3Amavedb%3Acalibration-b18c5122-57a0-4d54-90a7-9297411219c2"
]
}
],
"hasEvidenceItems": [
{
"type": "ExperimentalVariantFunctionalImpactStudyResult",
"description": "Variant effect study result for urn:mavedb:00000096-a-1#2446.",
"specifiedBy": {
"type": "Method",
"name": "Experimental protocol",
"reportedIn": "http://www.ncbi.nlm.nih.gov/pubmed/37101203"
},
"contributions": [
{
"type": "Contribution",
"name": "MaveDB API",
"description": "Contribution from the MaveDB API",
"contributor": {
"type": "Agent",
"name": "MaveDB API",
"description": "MaveDB API agent, version 2026.2.5",
"extensions": [
{
"name": "mavedbApiVersion",
"value": "2026.2.5"
}
],
"agentType": "Software"
},
"activityType": "software application programming interface",
"date": "2026-06-24 18:44:14.486748"
},
{
"type": "Contribution",
"name": "MaveDB VRS Mapper",
"description": "Contribution from the MaveDB VRS mapping software",
"contributor": {
"type": "Agent",
"name": "MaveDB VRS Mapping Agent",
"description": "MaveDB VRS mapping agent, version 2026.2.0",
"extensions": [
{
"name": "mavedbVrsVersion",
"value": "2026.2.0"
}
],
"agentType": "Software"
},
"activityType": "human genome sequence mapping process",
"date": "2026-05-28 00:00:00"
},
{
"type": "Contribution",
"name": "MaveDB Dataset Creator",
"description": "When this resource was first submitted, and by whom.",
"extensions": [
{
"name": "resourceType",
"value": "Variant"
}
],
"contributor": {
"type": "Agent",
"name": "0000-0001-5034-1952",
"description": "MaveDB ORCid authenticated user 0000-0001-5034-1952",
"agentType": "Person"
},
"activityType": "http://purl.obolibrary.org/obo/CRO_0000105",
"date": "2022-03-18 00:00:00"
},
{
"type": "Contribution",
"name": "MaveDB Dataset Modifier",
"description": "When this resource was last modified, and by whom.",
"extensions": [
{
"name": "resourceType",
"value": "Variant"
}
],
"contributor": {
"type": "Agent",
"name": "0000-0001-5034-1952",
"description": "MaveDB ORCid authenticated user 0000-0001-5034-1952",
"agentType": "Person"
},
"activityType": "http://purl.obolibrary.org/obo/CRO_0000103",
"date": "2022-06-14 00:00:00"
}
],
"reportedIn": [
"https://mavedb.org/score-sets/urn:mavedb:00000096-a-1?variant=urn%3Amavedb%3A00000096-a-1%232446",
"https://mavedb.org/variant/PA2579976630"
],
"sourceDataSet": {
"id": "urn:mavedb:00000096-a-1",
"type": "DataSet",
"name": "GCK activity measured by complementation",
"description": "Activity of GCK variants measured by functional complementation of an hxk1\u0394hxk2\u0394glk1\u0394 yeast strain.",
"reportedIn": "https://mavedb.org/score-sets/urn:mavedb:00000096-a-1",
"releaseDate": "2022-06-14",
"license": {
"name": "CC0 (Public domain)",
"primaryCoding": {
"system": "https://spdx.org/licenses/",
"systemVersion": "1.0",
"code": "CC0-1.0",
"iris": [
"https://creativecommons.org/publicdomain/zero/1.0/"
]
}
}
},
"focusVariant": {
"id": "ga4gh:VA.uKdR7fpiG9_r42oyAC33xQyd24VUNW3I",
"type": "Allele",
"extensions": [
{
"name": "vrs_ref_allele_seq",
"value": "F"
}
],
"digest": "uKdR7fpiG9_r42oyAC33xQyd24VUNW3I",
"expressions": [
{
"syntax": "hgvs.p",
"value": "NP_000153.1:p.Phe269Gln"
}
],
"location": {
"id": "ga4gh:SL.mr0SP5seWdgAplFqdmHBAbdhfmPcalZq",
"type": "SequenceLocation",
"digest": "mr0SP5seWdgAplFqdmHBAbdhfmPcalZq",
"sequenceReference": {
"type": "SequenceReference",
"refgetAccession": "SQ._mgLuM2tl_ap4JfYxyyr96JzV_FxAqsk"
},
"start": 268,
"end": 269
},
"state": {
"type": "LiteralSequenceExpression",
"sequence": "Q"
}
},
"functionalImpactScore": 0.21223874
}
],
"directionOfEvidenceProvided": "supports",
"evidenceOutcome": {
"primaryCoding": {
"system": "ga4gh-gks-term:experimental-var-func-impact-classification",
"code": "abnormal"
}
}
}
]
}
],
"directionOfEvidenceProvided": "supports",
"strengthOfEvidenceProvided": {
"primaryCoding": {
"system": "ACMG Guidelines, 2015",
"code": "moderate"
}
},
"evidenceOutcome": {
"name": "ACMG 2015 PS3 Criterion Met",
"primaryCoding": {
"system": "ACMG Guidelines, 2015",
"code": "PS3_moderate"
}
}
},
{
"type": "EvidenceLine",
"description": "Pathogenicity evidence line for urn:mavedb:00000096-a-1#2446.",
"extensions": [
{
"name": "Containing classification name",
"value": "Decreased activity",
"description": "The name of the classification which contains this variant."
}
],
"specifiedBy": {
"type": "Method",
"name": "Calibration method",
"methodType": "PS3",
"reportedIn": "Not Provided"
},
"contributions": [
{
"type": "Contribution",
"name": "MaveDB API",
"description": "Contribution from the MaveDB API",
"contributor": {
"type": "Agent",
"name": "MaveDB API",
"description": "MaveDB API agent, version 2026.2.5",
"extensions": [
{
"name": "mavedbApiVersion",
"value": "2026.2.5"
}
],
"agentType": "Software"
},
"activityType": "software application programming interface",
"date": "2026-06-24 18:44:14.755802"
},
{
"type": "Contribution",
"name": "MaveDB VRS Mapper",
"description": "Contribution from the MaveDB VRS mapping software",
"contributor": {
"type": "Agent",
"name": "MaveDB VRS Mapping Agent",
"description": "MaveDB VRS mapping agent, version 2026.2.0",
"extensions": [
{
"name": "mavedbVrsVersion",
"value": "2026.2.0"
}
],
"agentType": "Software"
},
"activityType": "human genome sequence mapping process",
"date": "2026-05-28 00:00:00"
},
{
"id": "urn:mavedb:calibration-c1472fe6-94f4-4785-b313-4777e9839f92",
"type": "Contribution",
"name": "IGVF Coding Variant Focus Group -- Controls: Missense Variants Only",
"description": "Contribution from a score calibration.",
"contributor": {
"type": "Agent",
"name": "AnonymousUser",
"description": "MaveDB ORCid authenticated user AnonymousUser",
"agentType": "Person"
},
"activityType": "variant specific calibration",
"date": "2025-11-14 00:00:00"
}
],
"reportedIn": [
{
"id": "urn:mavedb:calibration-c1472fe6-94f4-4785-b313-4777e9839f92",
"type": "Document",
"name": "MaveDB Score Calibration",
"extensions": [
{
"name": "Baseline score",
"value": 1.0,
"description": "No description for this baseline score provided."
},
{
"name": "Research use only",
"value": false,
"description": "Indicates whether this score calibration is intended for research use only."
},
{
"name": "Primary calibration",
"value": false,
"description": "Indicates whether this score calibration is the primary calibration for its associated score set."
},
{
"name": "Investigator provided",
"value": false,
"description": "Indicates whether this score calibration was provided by the investigator rather than generated by MaveDB."
},
{
"name": "Decreased activity",
"value": [
null,
0.66
],
"description": "No description for this functional classification provided."
},
{
"name": "Hyperactive",
"value": [
1.18,
null
],
"description": "No description for this functional classification provided."
},
{
"name": "(0.66,1.18)",
"value": [
0.66,
1.18
],
"description": "No description for this functional classification provided."
}
],
"documentType": "score calibration",
"title": "IGVF Coding Variant Focus Group -- Controls: Missense Variants Only",
"urls": [
"https://mavedb.org/score-sets/urn:mavedb:00000096-a-1/calibrations?calibration=urn%3Amavedb%3Acalibration-c1472fe6-94f4-4785-b313-4777e9839f92"
]
}
],
"targetProposition": {
"type": "VariantPathogenicityProposition",
"description": "Variant pathogenicity proposition for urn:mavedb:00000096-a-1#2446.",
"subjectVariant": {
"id": "ga4gh:VA.uKdR7fpiG9_r42oyAC33xQyd24VUNW3I",
"type": "Allele",
"extensions": [
{
"name": "vrs_ref_allele_seq",
"value": "F"
}
],
"digest": "uKdR7fpiG9_r42oyAC33xQyd24VUNW3I",
"expressions": [
{
"syntax": "hgvs.p",
"value": "NP_000153.1:p.Phe269Gln"
}
],
"location": {
"id": "ga4gh:SL.mr0SP5seWdgAplFqdmHBAbdhfmPcalZq",
"type": "SequenceLocation",
"digest": "mr0SP5seWdgAplFqdmHBAbdhfmPcalZq",
"sequenceReference": {
"type": "SequenceReference",
"refgetAccession": "SQ._mgLuM2tl_ap4JfYxyyr96JzV_FxAqsk"
},
"start": 268,
"end": 269
},
"state": {
"type": "LiteralSequenceExpression",
"sequence": "Q"
}
},
"geneContextQualifier": {
"primaryCoding": {
"system": "https://www.genenames.org/",
"code": "GCK"
}
},
"predicate": "isCausalFor",
"objectCondition": {
"conceptType": "Disease",
"primaryCoding": {
"system": "https://www.ncbi.nlm.nih.gov/medgen/",
"code": "C0012634",
"iris": [
"http://identifiers.org/medgen/C0012634"
]
}
}
},
"hasEvidenceItems": [
{
"type": "Statement",
"description": "Variant functional impact statement for urn:mavedb:00000096-a-1#2446.",
"specifiedBy": {
"type": "Method",
"name": "Variant interpretation guideline",
"reportedIn": "https://pubmed.ncbi.nlm.nih.gov/29785012/"
},
"contributions": [
{
"type": "Contribution",
"name": "MaveDB API",
"description": "Contribution from the MaveDB API",
"contributor": {
"type": "Agent",
"name": "MaveDB API",
"description": "MaveDB API agent, version 2026.2.5",
"extensions": [
{
"name": "mavedbApiVersion",
"value": "2026.2.5"
}
],
"agentType": "Software"
},
"activityType": "software application programming interface",
"date": "2026-06-24 18:44:14.755708"
},
{
"type": "Contribution",
"name": "MaveDB VRS Mapper",
"description": "Contribution from the MaveDB VRS mapping software",
"contributor": {
"type": "Agent",
"name": "MaveDB VRS Mapping Agent",
"description": "MaveDB VRS mapping agent, version 2026.2.0",
"extensions": [
{
"name": "mavedbVrsVersion",
"value": "2026.2.0"
}
],
"agentType": "Software"
},
"activityType": "human genome sequence mapping process",
"date": "2026-05-28 00:00:00"
},
{
"id": "urn:mavedb:calibration-c1472fe6-94f4-4785-b313-4777e9839f92",
"type": "Contribution",
"name": "IGVF Coding Variant Focus Group -- Controls: Missense Variants Only",
"description": "Contribution from a score calibration.",
"contributor": {
"type": "Agent",
"name": "AnonymousUser",
"description": "MaveDB ORCid authenticated user AnonymousUser",
"agentType": "Person"
},
"activityType": "variant specific calibration",
"date": "2025-11-14 00:00:00"
}
],
"proposition": {
"type": "ExperimentalVariantFunctionalImpactProposition",
"description": "Variant functional impact proposition for urn:mavedb:00000096-a-1#2446.",
"subjectVariant": {
"id": "ga4gh:VA.uKdR7fpiG9_r42oyAC33xQyd24VUNW3I",
"type": "Allele",
"extensions": [
{
"name": "vrs_ref_allele_seq",
"value": "F"
}
],
"digest": "uKdR7fpiG9_r42oyAC33xQyd24VUNW3I",
"expressions": [
{
"syntax": "hgvs.p",
"value": "NP_000153.1:p.Phe269Gln"
}
],
"location": {
"id": "ga4gh:SL.mr0SP5seWdgAplFqdmHBAbdhfmPcalZq",
"type": "SequenceLocation",
"digest": "mr0SP5seWdgAplFqdmHBAbdhfmPcalZq",
"sequenceReference": {
"type": "SequenceReference",
"refgetAccession": "SQ._mgLuM2tl_ap4JfYxyyr96JzV_FxAqsk"
},
"start": 268,
"end": 269
},
"state": {
"type": "LiteralSequenceExpression",
"sequence": "Q"
}
},
"predicate": "impactsFunctionOf",
"objectSequenceFeature": {
"primaryCoding": {
"system": "https://www.genenames.org/",
"code": "GCK"
}
},
"experimentalContextQualifier": {
"id": "urn:mavedb:00000096-a",
"type": "Document",
"name": "MaveDB Experiment",
"description": "Activity of GCK variants measured by functional complementation of an hxk1\u0394hxk2\u0394glk1\u0394 yeast strain.",
"documentType": "experiment",
"title": "GCK activity measured by complementation",
"urls": [
"https://mavedb.org/experiments/urn:mavedb:00000096-a"
]
}
},
"direction": "supports",
"classification": {
"primaryCoding": {
"system": "ga4gh-gks-term:experimental-var-func-impact-classification",
"code": "abnormal"
}
},
"hasEvidenceLines": [
{
"type": "EvidenceLine",
"description": "Functional evidence line for urn:mavedb:00000096-a-1#2446",
"extensions": [
{
"name": "Containing functional classification",
"value": "Decreased activity",
"description": "The functional classification which contains this variant."
}
],
"specifiedBy": {
"type": "Method",
"name": "Calibration method",
"reportedIn": "http://www.ncbi.nlm.nih.gov/pubmed/37101203"
},
"contributions": [
{
"type": "Contribution",
"name": "MaveDB API",
"description": "Contribution from the MaveDB API",
"contributor": {
"type": "Agent",
"name": "MaveDB API",
"description": "MaveDB API agent, version 2026.2.5",
"extensions": [
{
"name": "mavedbApiVersion",
"value": "2026.2.5"
}
],
"agentType": "Software"
},
"activityType": "software application programming interface",
"date": "2026-06-24 18:44:14.755510"
},
{
"type": "Contribution",
"name": "MaveDB VRS Mapper",
"description": "Contribution from the MaveDB VRS mapping software",
"contributor": {
"type": "Agent",
"name": "MaveDB VRS Mapping Agent",
"description": "MaveDB VRS mapping agent, version 2026.2.0",
"extensions": [
{
"name": "mavedbVrsVersion",
"value": "2026.2.0"
}
],
"agentType": "Software"
},
"activityType": "human genome sequence mapping process",
"date": "2026-05-28 00:00:00"
},
{
"id": "urn:mavedb:calibration-c1472fe6-94f4-4785-b313-4777e9839f92",
"type": "Contribution",
"name": "IGVF Coding Variant Focus Group -- Controls: Missense Variants Only",
"description": "Contribution from a score calibration.",
"contributor": {
"type": "Agent",
"name": "AnonymousUser",
"description": "MaveDB ORCid authenticated user AnonymousUser",
"agentType": "Person"
},
"activityType": "variant specific calibration",
"date": "2025-11-14 00:00:00"
}
],
"reportedIn": [
{
"id": "urn:mavedb:calibration-c1472fe6-94f4-4785-b313-4777e9839f92",
"type": "Document",
"name": "MaveDB Score Calibration",
"extensions": [
{
"name": "Baseline score",
"value": 1.0,
"description": "No description for this baseline score provided."
},
{
"name": "Research use only",
"value": false,
"description": "Indicates whether this score calibration is intended for research use only."
},
{
"name": "Primary calibration",
"value": false,
"description": "Indicates whether this score calibration is the primary calibration for its associated score set."
},
{
"name": "Investigator provided",
"value": false,
"description": "Indicates whether this score calibration was provided by the investigator rather than generated by MaveDB."
},
{
"name": "Decreased activity",
"value": [
null,
0.66
],
"description": "No description for this functional classification provided."
},
{
"name": "Hyperactive",
"value": [
1.18,
null
],
"description": "No description for this functional classification provided."
},
{
"name": "(0.66,1.18)",
"value": [
0.66,
1.18
],
"description": "No description for this functional classification provided."
}
],
"documentType": "score calibration",
"title": "IGVF Coding Variant Focus Group -- Controls: Missense Variants Only",
"urls": [
"https://mavedb.org/score-sets/urn:mavedb:00000096-a-1/calibrations?calibration=urn%3Amavedb%3Acalibration-c1472fe6-94f4-4785-b313-4777e9839f92"
]
}
],
"hasEvidenceItems": [
{
"type": "ExperimentalVariantFunctionalImpactStudyResult",
"description": "Variant effect study result for urn:mavedb:00000096-a-1#2446.",
"specifiedBy": {
"type": "Method",
"name": "Experimental protocol",
"reportedIn": "http://www.ncbi.nlm.nih.gov/pubmed/37101203"
},
"contributions": [
{
"type": "Contribution",
"name": "MaveDB API",
"description": "Contribution from the MaveDB API",
"contributor": {
"type": "Agent",
"name": "MaveDB API",
"description": "MaveDB API agent, version 2026.2.5",
"extensions": [
{
"name": "mavedbApiVersion",
"value": "2026.2.5"
}
],
"agentType": "Software"
},
"activityType": "software application programming interface",
"date": "2026-06-24 18:44:14.486748"
},
{
"type": "Contribution",
"name": "MaveDB VRS Mapper",
"description": "Contribution from the MaveDB VRS mapping software",
"contributor": {
"type": "Agent",
"name": "MaveDB VRS Mapping Agent",
"description": "MaveDB VRS mapping agent, version 2026.2.0",
"extensions": [
{
"name": "mavedbVrsVersion",
"value": "2026.2.0"
}
],
"agentType": "Software"
},
"activityType": "human genome sequence mapping process",
"date": "2026-05-28 00:00:00"
},
{
"type": "Contribution",
"name": "MaveDB Dataset Creator",
"description": "When this resource was first submitted, and by whom.",
"extensions": [
{
"name": "resourceType",
"value": "Variant"
}
],
"contributor": {
"type": "Agent",
"name": "0000-0001-5034-1952",
"description": "MaveDB ORCid authenticated user 0000-0001-5034-1952",
"agentType": "Person"
},
"activityType": "http://purl.obolibrary.org/obo/CRO_0000105",
"date": "2022-03-18 00:00:00"
},
{
"type": "Contribution",
"name": "MaveDB Dataset Modifier",
"description": "When this resource was last modified, and by whom.",
"extensions": [
{
"name": "resourceType",
"value": "Variant"
}
],
"contributor": {
"type": "Agent",
"name": "0000-0001-5034-1952",
"description": "MaveDB ORCid authenticated user 0000-0001-5034-1952",
"agentType": "Person"
},
"activityType": "http://purl.obolibrary.org/obo/CRO_0000103",
"date": "2022-06-14 00:00:00"
}
],
"reportedIn": [
"https://mavedb.org/score-sets/urn:mavedb:00000096-a-1?variant=urn%3Amavedb%3A00000096-a-1%232446",
"https://mavedb.org/variant/PA2579976630"
],
"sourceDataSet": {
"id": "urn:mavedb:00000096-a-1",
"type": "DataSet",
"name": "GCK activity measured by complementation",
"description": "Activity of GCK variants measured by functional complementation of an hxk1\u0394hxk2\u0394glk1\u0394 yeast strain.",
"reportedIn": "https://mavedb.org/score-sets/urn:mavedb:00000096-a-1",
"releaseDate": "2022-06-14",
"license": {
"name": "CC0 (Public domain)",
"primaryCoding": {
"system": "https://spdx.org/licenses/",
"systemVersion": "1.0",
"code": "CC0-1.0",
"iris": [
"https://creativecommons.org/publicdomain/zero/1.0/"
]
}
}
},
"focusVariant": {
"id": "ga4gh:VA.uKdR7fpiG9_r42oyAC33xQyd24VUNW3I",
"type": "Allele",
"extensions": [
{
"name": "vrs_ref_allele_seq",
"value": "F"
}
],
"digest": "uKdR7fpiG9_r42oyAC33xQyd24VUNW3I",
"expressions": [
{
"syntax": "hgvs.p",
"value": "NP_000153.1:p.Phe269Gln"
}
],
"location": {
"id": "ga4gh:SL.mr0SP5seWdgAplFqdmHBAbdhfmPcalZq",
"type": "SequenceLocation",
"digest": "mr0SP5seWdgAplFqdmHBAbdhfmPcalZq",
"sequenceReference": {
"type": "SequenceReference",
"refgetAccession": "SQ._mgLuM2tl_ap4JfYxyyr96JzV_FxAqsk"
},
"start": 268,
"end": 269
},
"state": {
"type": "LiteralSequenceExpression",
"sequence": "Q"
}
},
"functionalImpactScore": 0.21223874
}
],
"directionOfEvidenceProvided": "supports",
"evidenceOutcome": {
"primaryCoding": {
"system": "ga4gh-gks-term:experimental-var-func-impact-classification",
"code": "abnormal"
}
}
}
]
}
],
"directionOfEvidenceProvided": "supports",
"strengthOfEvidenceProvided": {
"primaryCoding": {
"system": "ACMG Guidelines, 2015",
"code": "moderate"
}
},
"evidenceOutcome": {
"name": "ACMG 2015 PS3 Criterion Met",
"primaryCoding": {
"system": "ACMG Guidelines, 2015",
"code": "PS3_moderate"
}
}
}
]
}
The tools used¶
- ga4gh-va-spec (
ga4gh-va-spec~0.4.2) — the VA-SpecStudyResult,Statement,EvidenceLine,Contribution, andDataSetmodels MaveDB populates across all three altitudes. - MaveDB API — generates and serves these VA-Spec annotations (the
MaveDB APIagent stamped into each statement'scontributions) alongside the underlying score-set data.
How to reuse this pattern¶
- VA-Spec specification — the statement and study-result model.
- Foundational vignette: Giving every MAVE variant a precise, computable identity with VRS — the
focusVariantthese statements point at. - MaveDB API source: VariantEffect/mavedb-api — where these VA-Spec statements are assembled and served.
- Related vignette: Annotating a variant once, across every score set — why one variant's evidence can draw on many experiments.