Is COCH p.Leu114Pro (c.341T>C) pathogenic?

COCH p.Leu114Pro (c.341T>C) is classified Pathogenic in COCH (ClinVar, Single submitter, 1 submitter; last evaluated 2020-09-30). AlphaMissense: likely pathogenic (0.6282); Absent from gnomAD v4.1; Associated with autosomal dominant nonsyndromic hearing loss 9.

What condition is associated with COCH p.Leu114Pro (c.341T>C)?

COCH p.Leu114Pro (c.341T>C) is associated with autosomal dominant nonsyndromic hearing loss 9 (ClinVar).

How common is COCH p.Leu114Pro (c.341T>C) in the general population?

COCH p.Leu114Pro (c.341T>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about COCH p.Leu114Pro (c.341T>C)?

AlphaMissense predicts likely pathogenic (score 0.6282) — an in-silico prediction, not a clinical call.

COCH p.Leu114Pro

c.341T>C · rs2138844314 · VCV1174533

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.6282 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

autosomal dominant nonsyndromic hearing loss 9

Computational evidence

Protein change
AlphaMissense	0.6282	likely pathogenic ✓ concordant with ClinVar
REVEL	0.857	moderately pathogenic-leaning
SaProt	LLR -12.80	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not looked up on this page · why
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	26.5	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.Leu114Pro
Coding: c.341T>C
dbSNP: rs2138844314
Type: single nucleotide variant
Location: chr14:30878912 (GRCh38)

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

Disease context

autosomal dominant nonsyndromic hearing loss 9 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

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-leu114pro (accessed [today's date]).

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