COCH p.Val262=
c.786A>G · rs375612298 · VCV504561
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 4 submitters
gnomAD v4.1
Rare
rare (popmax 0.112%, 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 0.46 | GERP -0.27, phastCons 0.94 |
| Overall | ||
| CADD | 12.97 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.112%
African / African-American · 84/75,050 alleles
Filtering AF
0.0926%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0855%
Overall
0.00595%
96/1,614,188 alleles · rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 0.112% | 893 |
| Admixed American | 0.00833% | 12,006 |
| Remaining individualsnot grpmax-eligible | 0.008% | 12,502 |
| European (non-Finnish) | 0.000169% | 590,005 |
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
- COCH
- Protein
- p.Val262=
- Coding
- c.786A>G
- MANE Select
- NM_004086
- dbSNP
- rs375612298
- Type
- single nucleotide variant
- Location
- chr14:30885446 (GRCh38)
- Gene constraint
- LOEUF 0.896 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 85.93 · 1 PDB
- Residue 262
- a UniProt-annotated variant site (in dfnb110); the vwfa 1 domain
Similar variants
- COCH p.Gly87Glu Likely pathogenic ★★★ same type
- COCH p.Pro51Ser Pathogenic ★★★ same type
- COCH p.Ala119Thr Uncertain significance ★★★ ⚠ same type
- COCH c.629+5C>T Benign ★★★ same type
- COCH p.Asp281Asn Benign ★★★ same type
- COCH p.Pro143= Benign ★★★ same type
- COCH c.1477+1G>C Likely pathogenic ★★ same type
- COCH p.Arg180Ter Pathogenic/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/coch-p-val262 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown