GJB2 p.Phe83fs
c.248_*825del · VCV3069173
Likely pathogenic
Single submitter
Classification
Likely pathogenic
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
Consequence
frameshift
predicted LoF
gnomAD v4.1
Rare
Conditions
1
nonsyndromic genetic hearing loss
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Consequence | frameshift | predicted loss-of-function |
|---|---|---|
| NMD | escapes | premature termination codon in the last exon (2 of 2) — the truncated protein is likely expressed. PVS1 input, not an applied code |
| Splicing | ||
| SpliceAI | — | not assessed · substitutions only |
| Constraint at this position | ||
| Conservation | phyloP -2.4 | GERP -3 |
Predicted loss-of-function is descriptive, not an applied PVS1 code.
Variant & gene context
- Gene
- GJB2
- Protein
- p.Phe83fs
- Coding
- c.248_*825del
- MANE Select
- NM_004004
- Type
- Deletion
- Location
- chr13:20188076 (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
Disease context
nonsyndromic genetic hearing loss — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatmentsFor Rare non-syndromic genetic deafness (Orphanet):
- Inheritance
- Autosomal dominant, Autosomal recessive, X-linked recessive
- Onset
- Infancy, Neonatal
Similar variants
- GJB2 p.Phe83Leu Benign/Likely benign ★★ ⚠ same residue
- GJB2 p.Phe83del Conflicting classifications of pathogenicity ★ same residue
- GJB2 p.Gly12fs Pathogenic ★★★ same condition
- GJB2 p.Leu56fs Pathogenic ★★★ same condition
- GJB2 p.Leu79fs Pathogenic ★★★ same condition
- GJB2 p.Gly11fs Pathogenic ★★ same condition
- GJB2 p.Lys112fs Pathogenic ★★ same condition
- GJB2 p.Val193fs Pathogenic/Likely pathogenic ★★ same condition
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-phe83fs (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown