COCH p.Ser400=
c.1200G>A · rs150529026 · VCV1396121
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.0227%, afr)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| REVEL | 0.132 | moderately benign-leaning |
|---|---|---|
| Splicing | ||
| SpliceAI | <0.2 | no splice effect predicted · four deltas, not one · how we know |
| Constraint at this position | ||
| Conservation | phyloP -0.59 | GERP -3.8 |
| Overall | ||
| CADD | 6.477 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0227%
African / African-American · 17/75,040 alleles
Filtering AF
0.0144%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0118%
Overall
0.00285%
46/1,614,170 alleles · ultra-rare
exomes 29/1,461,888 · genomes 17/152,282 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 0.0227% | 4,414 |
| Middle Eastern | 0.0165% | 6,062 |
| Admixed American | 0.0117% | 8,574 |
| East Asian | 0.00668% | 14,961 |
| Remaining individualsnot grpmax-eligible | 0.0064% | 15,626 |
| South Asian | 0.00329% | 30,363 |
| European (non-Finnish) | 0.000932% | 107,276 |
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.Ser400=
- Coding
- c.1200G>A
- MANE Select
- NM_004086
- dbSNP
- rs150529026
- Type
- single nucleotide variant
- Location
- chr14:30886035 (GRCh38)
- Gene constraint
- LOEUF 0.896 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 85.93 · 1 PDB
- Residue 400
- 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-ser400 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown