GJB2 p.Val84=
c.252G>A · rs2500251805 · VCV2746198
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Absent
absent from gnomAD v4.1
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP -0.1 | GERP -3.9, phastCons 0.48 |
| Overall | ||
| CADD | 4.722 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.
Variant & gene context
- Gene
- GJB2
- Protein
- p.Val84=
- Coding
- c.252G>A
- MANE Select
- NM_004004
- dbSNP
- rs2500251805
- Type
- single nucleotide variant
- Location
- chr13:20189330 (GRCh38)
- Gene constraint
- LOEUF 1.965 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
- Structure
- AlphaFold pLDDT 86.35 · 24 PDB
- Residue 84
- a UniProt-annotated variant site (in dfnb1a); a UniProt-annotated variant site (in dfnb1a; sorted to the plasma membrane normally and forms gap junctions that were morphologically and electrically indistinguishable from those of control; the mutation reduces the permeability of gjb2 gap junction channels to inositol 1,4,5-trisphosphate (ins(1,4,5)p3), resulting in blockade of the ins(1,4,5)p3-induced inward calcium current in neighboring cells); a UniProt-annotated variant site (in dfnb1a; the mutant disrupts cellular communication); an α-helix
Similar variants
- GJB2 p.Val84Leu Pathogenic ★★ same residue
- GJB2 p.Val84Met Pathogenic ★★ same residue
- GJB2 p.Val84Ala Likely pathogenic ★ same residue
- GJB2 c.-22-2A>C Likely pathogenic ★★★ same type
- GJB2 p.Gly12Cys Likely pathogenic ★★★ ⚠ same type
- GJB2 p.Leu76Pro Likely pathogenic ★★★ same type
- GJB2 p.Lys188Arg Likely pathogenic ★★★ same type
- GJB2 p.Met195Thr Likely pathogenic ★★★ same type
Built on 18 open, versioned datasets — ClinVar, gnomAD, AlphaMissense, REVEL, ClinGen & more — plus Sugi Variant's own cross-source analysis. Source data 2026-01–2026-10, ClinVar 2026-10. Full sources & versions →
Cite Sugi Variant
Gür T. Sugi Variant: A Deterministic Per-Variant Germline Reference from a Knowledge Graph for Humans and AI Agents. 2026. doi:10.5281/zenodo.21509445. This variant: https://sugi.bio/variant/gjb2-p-val84 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown