ACMG Pathogenicity Statement with Evidence — detailed example

ex:Statement001

A real ClinGen classification illustrating this structure: the root Statement, its population-frequency Evidence Line, and that line's Study Result. Source: ClinGen Hearing Loss VCEP classification of MYO15A:c.4642G>A (erepo). Three further Evidence Lines this classification also relies on (PM3_Strong, PS3_Supporting, PP3) are omitted here for space.

name: "ClinGen Hearing Loss

Expert Panel (OTOF/

specifiedBy

VariantPathogenicity-
Statement

ex:Statement001

proposition: ex:Proposition001

direction: "supports"

strength: "likely"

classification: "likely pathogenic"

proposition: ex:Variant001 isCausalFor "Autosomal recessive nonsyndromic hearing loss 3" — strength/outcome coded per ACMG Guidelines, 2015. ClinVar SCV007126591.1.

contributions

contributor: "ClinGen Hearing

activityType: "evaluated"

date: 2025-12-19

First in ClinVar 2025-12-20.

hasEvidenceLines 0..m

methodType: "population_data_

specifiedBy

«EvidenceLine»

VariantPathogenicity-
EvidenceLine

ex:EvidenceLine001

targetProposition: ex:Proposition001

directionOfEvidenceProvided: "supports"

strengthOfEvidenceProvided: "supporting"

evidenceOutcome: "PM2_supporting"

targetProposition references the same Proposition001 as the root Statement (explicit here, though omission would imply the same). evidenceOutcome names the ACMG criterion met, adjusted down from PM2's default "moderate" strength.

contributions

contributor: "curator001"

activityType: "evidence

hasEvidenceItems 0..m

name: "gnomAD methods"

reportedIn: "gnomAD help documentation"

specifiedBy

«StudyResult»

CohortAllele-
FrequencyStudyResult

ex:StudyResult001

focus: ex:Variant001

alleleFrequency: "0.005% (76/

sourceDataSet: "gnomAD v4"

this box's type is literally "CohortAlleleFrequencyStudyResult" — unlike Statement/EvidenceLine, Base Profile objects carry their own specific type rather than the base class name.

cohort

name: "European

cohort is CohortAlleleFrequencyStudyResult-specific — not a base StudyResult field.

TUTrial Use