GJB2 p.Phe83=
c.249C>T · rs111033218 · VCV1081025
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.00659%, sas)
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 -4.3 | GERP -3.9 |
| Overall | ||
| CADD | 0.57 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00659%
South Asian · 6/91,078 alleles
Filtering AF
0.00286%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00195%
Overall
0.00136%
22/1,614,090 alleles · very rare
exomes 22/1,461,800 · genomes 0/152,290 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| South Asiangrpmax | 0.00659% | 15,180 |
| Admixed American | 0.00333% | 30,012 |
| African / African-American | 0.00267% | 37,520 |
| East Asian | 0.00223% | 44,874 |
| European (non-Finnish) | 0.000932% | 107,276 |
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.Phe83=
- Coding
- c.249C>T
- MANE Select
- NM_004004
- dbSNP
- rs111033218
- Type
- single nucleotide variant
- Location
- chr13:20189333 (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 83
- a UniProt-annotated variant site (in dfnb1a); a UniProt-annotated variant site (in); an α-helix
Similar variants
- GJB2 p.Phe83Leu Benign/Likely benign ★★ ⚠ same residue
- GJB2 p.Phe83fs Likely pathogenic ★ same residue
- GJB2 p.Phe83del Conflicting classifications of pathogenicity ★ 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-phe83 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown