COCH p.Ile282=
c.846C>T · rs368609319 · VCV1207717
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
ultra-rare (popmax 0.0133%, amr)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| REVEL | 0.183 | benign-leaning |
|---|---|---|
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
| Constraint at this position | ||
| Conservation | phyloP -3.4 | GERP -3.2 |
| Overall | ||
| CADD | 5.723 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0133%
Admixed American · 8/60,010 alleles
Filtering AF
0.00676%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00522%
Overall
0.00279%
45/1,613,228 alleles · ultra-rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Admixed Americangrpmax | 0.0133% | 7,501 |
| South Asian | 0.0121% | 8,279 |
| Remaining individualsnot grpmax-eligible | 0.008% | 12,492 |
| African / African-American | 0.004% | 25,001 |
| European (non-Finnish) | 0.00153% | 65,511 |
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.Ile282=
- Coding
- c.846C>T
- MANE Select
- NM_004086
- dbSNP
- rs368609319
- Type
- single nucleotide variant
- Location
- chr14:30885506 (GRCh38)
- Gene constraint
- LOEUF 0.896 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 85.93 · 1 PDB
- Residue 282
- 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-ile282 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown