COCH p.Asn243=
c.729T>C · rs765692468 · VCV1982694
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.0783%, eas)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| REVEL | 0.16 | moderately benign-leaning |
|---|---|---|
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
| Constraint at this position | ||
| Conservation | phyloP -0.42 | GERP -3.8, phastCons 0.14 |
| Overall | ||
| CADD | 11.38 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0783%
East Asian · 35/44,718 alleles
Filtering AF
0.0578%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0508%
Overall
0.00275%
44/1,598,588 alleles · ultra-rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| East Asiangrpmax | 0.0783% | 1,278 |
| Remaining individualsnot grpmax-eligible | 0.00485% | 20,639 |
| European (non-Finnish) | 0.000515% | 194,345 |
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.Asn243=
- Coding
- c.729T>C
- MANE Select
- NM_004086
- dbSNP
- rs765692468
- Type
- single nucleotide variant
- Location
- chr14:30884652 (GRCh38)
- Gene constraint
- LOEUF 0.896 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 85.93 · 1 PDB
- Residue 243
- 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-asn243 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown