GJB2 p.Arg32Pro
c.95G>C · VCV4076581
Conflicting classifications of pathogenicity
Conflicting submitters
Classification
Conflicting classifications of pathogenicity
ClinVar
Review
Conflicting submitters ★☆☆☆
ClinVar · 2 submitters
AlphaMissense
likely pathogenic
0.9958 · ACMG-weighted
gnomAD v4.1
Absent
absent from gnomAD v4.1
Missense predictors
3/3 damaging
AlphaMissense, REVEL, SaProt
Computational evidence
| Protein change | ||
| AlphaMissense | 0.9958 | likely pathogenic · top 5% in GJB2 |
|---|---|---|
| REVEL | 0.975 | strongly pathogenic-leaning |
| SaProt | LLR -12.57 | damaging |
| ⇒ AlphaMissense, REVEL and SaProt all call this damaging. | ||
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
| Constraint at this position | ||
| Conservation | phyloP 7.7 | GERP 2, phastCons 1 |
| Regional constraint | o/e 0.98 | unconstrained · MANE · 677 bp · p 0.74 · regional, not allelic |
| Overall | ||
| CADD | 27.3 | PHRED · no single calibrated threshold — expert panels disagree |
AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.
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.Arg32Pro
- Coding
- c.95G>C
- MANE Select
- NM_004004
- Type
- single nucleotide variant
- Location
- chr13:20189487 (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 32
- a UniProt-annotated variant site (in dfnb1a); a UniProt-annotated variant site (in); an α-helix
Similar variants
- GJB2 p.Arg32Cys Pathogenic ★★ same residue
- GJB2 p.Arg32His Pathogenic ★★ same residue
- GJB2 p.Arg32Leu Pathogenic/Likely pathogenic ★★ same residue
- GJB2 p.Arg32Ser Pathogenic ★★ same residue
- GJB2 p.Arg32fs Pathogenic/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
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-arg32pro (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown