Evidence Repository - Clinical Genome Resources

The ClinGen Evidence Repository is an FDA-recognized human genetic variant database containing expert-curated assertions regarding variants' pathogenicity and supporting evidence summaries. [Disclaimer]

Variant: NM_004004.6(GJB2):c.109G>T (p.Val37Phe)

CA273605

179256 (ClinVar)

Gene: GJB2 (HGNC:2706)

Condition: nonsyndromic genetic deafness (MONDO:0019497)

Inheritance Mode: Autosomal recessive inheritance

UUID: 8ce5aea1-5ed1-4071-bd6b-1a3d6b2f1821

Approved on: 2026-08-19

Published on: 2026-09-30

HGVS expressions

NM_004004.6(GJB2):c.109G>T (p.Val37Phe)

NM_004004.6:c.109G>T

NC_000013.11:g.20189473C>A

CM000675.2:g.20189473C>A

NC_000013.10:g.20763612C>A

CM000675.1:g.20763612C>A

NC_000013.9:g.19661612C>A

NG_008358.1:g.8503G>T

ENST00000382844.2:c.109G>T

ENST00000382848.5:c.109G>T

ENST00000382844.1:c.109G>T

ENST00000382848.4:c.109G>T

NM_004004.5:c.109G>T

Likely Pathogenic

PP3 PM3 PM5 PM2_Supporting

Evidence Links 0

Expert Panel

Hearing Loss VCEP

Criteria Specification Information

Criteria Specification: ClinGen Hearing Loss Expert Panel Specifications to the ACMG/AMP Variant Interpretation Guidelines for CDH23, COCH, GJB2, KCNQ4, MYO6, MYO7A, SLC26A4, TECTA and USH2A Version 2.0

PDF

Criteria Specification Approval History

Criteria Specifications for this VCEP

Evidence submitted by expert panel

Hearing Loss VCEP

The NM_004004.6(GJB2):c.109G>T variant in GJB2 is a missense variant predicted to cause substitution of Valine to Phenylalanine at amino acid 37 (p.Val37Phe). This variant is absent from gnomAD v4.1.1 (PM2_Supporting met). The computational predictor REVEL yields a score of 0.828 (PP3 met).This variant has been detected in one individual with hearing loss in trans with a pathogenic c.167del (p.Leu56Argfs*26) (Laboratory for Molecular Medicine internal data, Clinvar ID 179256) (1.0 point, PM3 met). One missense variant, p.Val37Ile (ClinVar ID 17023), in the same codon has been classified as pathogenic for autosomal recessive non syndromic hearing loss by the ClinGen HL-VCEP (PM5 met). In summary, based on the current evidence (PM2_Supporting, PM3, PM5, PP3), the variant NM_004004.6(GJB2):c.109G>T (p.Val37Phe) is classified as likely pathogenic for autosomal recessive non-syndromic HL based on the ACMG/AMP criteria applied, as specified by the ClinGen Hearing Loss VCEP. (ClinGen Hearing Loss VCEP specifications version 2; 8/19/2026).

PP3

The computational predictor REVEL yields a score of 0.828.

PM3

This variant has been detected in 1 individual with hearing loss, compound heterozygous for this variant and a loss of function variant (Laboratory for molecular medicine, Clinvar ID 179256) (PM3).

PM5

One missense variant, p.Val37Ile (ClinVar ID 17023), in the same codon has been classified as pathogenic for autosomal recessive non syndromic hearing loss by the ClinGen HL-VCEP.

PM2_Supporting

This variant is absent from gnomAD v4.1.1.

Curation History

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