GJB2 p.Arg75=
c.225G>T · rs149137695 · VCV1134451
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
ultra-rare (popmax 0.036%, afr)
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 -5.8 | GERP -3.9 |
| Overall | ||
| CADD | 0.735 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.036%
African / African-American · 27/74,928 alleles
Filtering AF
0.0254%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0219%
Overall
0.00167%
27/1,614,074 alleles · ultra-rare
exomes 9/1,461,858 · genomes 18/152,216 · joint denominator
Rarity supports pathogenicity (ACMG PM2); frequency above a disease-specific BA1/BS1 threshold argues against it. A variant frequent in one ancestry group can be near-absent in others, so a single global figure can mislead.
Variant & gene context
- Gene
- GJB2
- Protein
- p.Arg75=
- Coding
- c.225G>T
- MANE Select
- NM_004004
- dbSNP
- rs149137695
- Type
- single nucleotide variant
- Location
- chr13:20189357 (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 75
- a UniProt-annotated variant site (in dfnb1a); a UniProt-annotated variant site (in ppkdfn; the mutant protein completely prevents the formation of functional channels); a UniProt-annotated variant site (in ppkdfn and dfna3a; does not affect protein trafficking; affects the ability to form functional channels; dominant negative effect); an α-helix
Similar variants
- GJB2 p.Arg75Gln Pathogenic ★★ same residue
- GJB2 p.Arg75Trp Pathogenic ★★ same residue
- GJB2 p.Arg75Gly 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-arg75 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown