COCH p.Ser425fs
c.1273del · VCV3376726
Pathogenic
Single submitter
Classification
Pathogenic
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
Consequence
frameshift
predicted LoF
gnomAD v4.1
Rare
Conditions
1
hearing loss, autosomal recessive 110
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Consequence | frameshift | predicted loss-of-function |
|---|---|---|
| NMD | predicted | premature termination codon in exon 11 of 12 |
| Splicing | ||
| SpliceAI | — | not assessed · substitutions only |
| Constraint at this position | ||
| Conservation | phyloP -4.2 | GERP -3.8 |
Predicted loss-of-function is descriptive, not an applied PVS1 code.
Variant & gene context
- Gene
- COCH
- Protein
- p.Ser425fs
- Coding
- c.1273del
- MANE Select
- NM_004086
- Type
- Deletion
- Location
- chr14:30886108 (GRCh38)
- Gene constraint
- LOEUF 0.896 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 85.93 · 1 PDB
- Residue 425
- a UniProt-annotated variant site (in dfnb110); the vwfa 2 domain
Similar variants
- COCH p.Ala432fs Uncertain significance ★ same condition
- COCH p.Arg180Ter Pathogenic/Likely pathogenic ★★ same condition
- COCH p.Arg98Ter Likely pathogenic ★★ same condition
- COCH p.Ser381delinsArgTer Pathogenic ★★ same condition
- COCH p.Arg180Gln Uncertain significance ★★ ⚠ same condition
- COCH c.*27A>T Benign ★★ same condition
- COCH p.Thr352Ser Benign ★★ same condition
- COCH p.Cys351Ter Likely pathogenic ★ same condition
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-ser425fs (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown