COCH p.Ala407=
c.1221T>C · rs199608109 · VCV667097
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 5 submitters
gnomAD v4.1
Rare
ultra-rare (popmax 0.0933%, amr)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| REVEL | 0.081 | moderately benign-leaning |
|---|---|---|
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
| Constraint at this position | ||
| Conservation | phyloP 0.17 | GERP -0.72, phastCons 0.99 |
| Overall | ||
| CADD | 13.68 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0933%
Admixed American · 56/60,032 alleles
Filtering AF
0.0737%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0667%
Overall
0.00353%
57/1,614,264 alleles · ultra-rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Admixed Americangrpmax | 0.0933% | 1,072 |
| Remaining individualsnot grpmax-eligible | 0.0016% | 62,512 |
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.Ala407=
- Coding
- c.1221T>C
- MANE Select
- NM_004086
- dbSNP
- rs199608109
- Type
- single nucleotide variant
- Location
- chr14:30886056 (GRCh38)
- Gene constraint
- LOEUF 0.896 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 85.93 · 1 PDB
- Residue 407
- a UniProt-annotated variant site (in dfnb110); the vwfa 2 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-ala407 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown