Is COCH p.Trp117Arg (c.349T>C) pathogenic?

COCH p.Trp117Arg (c.349T>C) is classified Pathogenic/Likely pathogenic in COCH (ClinVar, Multiple submitters, 5 submitters; last evaluated 2026-03-09). AlphaMissense: likely pathogenic (0.9818); Absent from gnomAD v4.1; Associated with Genetic hearing loss.

What condition is associated with COCH p.Trp117Arg (c.349T>C)?

COCH p.Trp117Arg (c.349T>C) is associated with Genetic hearing loss, autosomal dominant nonsyndromic hearing loss 9 (ClinVar).

How common is COCH p.Trp117Arg (c.349T>C) in the general population?

COCH p.Trp117Arg (c.349T>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about COCH p.Trp117Arg (c.349T>C)?

AlphaMissense predicts likely pathogenic (score 0.9818) — an in-silico prediction, not a clinical call.

COCH p.Trp117Arg

c.349T>C · rs121908929 · VCV6610

Pathogenic/Likely pathogenic Multiple submitters

Classification

Pathogenic/Likely pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 5 submitters

AlphaMissense

likely pathogenic

0.9818 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Genetic hearing loss

Computational evidence

Protein change
AlphaMissense	0.9818	likely pathogenic ✓ concordant with ClinVar · top 8% in COCH
REVEL	0.85	moderately pathogenic-leaning
SaProt	LLR -11.21	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · T>A here scores Δ0.40 · evaluated, not missing
Constraint at this position
Conservation	phyloP 7.9	GERP 1.9, phastCons 1
Regional constraint	o/e 0.90	unconstrained · MANE · 15 kb · p 0.0071 · regional, not allelic
Overall
CADD	25.9	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: COCH
Protein: p.Trp117Arg
Coding: c.349T>C
MANE Select: NM_004086
dbSNP: rs121908929
Type: single nucleotide variant
Location: chr14:30878920 (GRCh38)
Gene constraint: LOEUF 0.896 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 85.93 · 1 PDB
Residue 117: a UniProt-annotated variant site (in dfnb110); the lccl domain; a UniProt-annotated variant site (in dfna9; does not affect protein deposition to the extracellular matrix)

Full COCH gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Genetic hearing loss — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: autosomal dominant nonsyndromic hearing loss 9

Similar variants

COCH p.Gly87Glu Likely pathogenic ★★★ same condition
COCH p.Pro51Ser Pathogenic ★★★ same condition
COCH p.Ala119Thr Uncertain significance ★★★ ⚠ same condition
COCH c.629+5C>T Benign ★★★ same condition
COCH p.Asp281Asn Benign ★★★ same condition
COCH p.Pro143= Benign ★★★ same condition
COCH p.Arg98Ter Likely pathogenic ★★ same condition
COCH p.Cys542Phe 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-trp117arg (accessed [today's date]).

Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown