Is COCH p.Ala247Val (c.740C>T) pathogenic?

COCH p.Ala247Val (c.740C>T) is classified Uncertain significance in COCH (ClinVar, Single submitter, 1 submitter; last evaluated 2023-12-16). AlphaMissense: likely pathogenic (0.8826); Absent from gnomAD v4.1; Associated with Inborn genetic diseases.

What condition is associated with COCH p.Ala247Val (c.740C>T)?

COCH p.Ala247Val (c.740C>T) is associated with Inborn genetic diseases (ClinVar).

How common is COCH p.Ala247Val (c.740C>T) in the general population?

COCH p.Ala247Val (c.740C>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about COCH p.Ala247Val (c.740C>T)?

AlphaMissense predicts likely pathogenic (score 0.8826) — an in-silico prediction, not a clinical call.

COCH p.Ala247Val

c.740C>T · rs749516210 · VCV3147065

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.8826 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.8826	likely pathogenic
REVEL	0.916	moderately pathogenic-leaning
SaProt	LLR -9.39	tolerated
⇒ AlphaMissense and REVEL call this damaging; SaProt does not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.7	GERP 1.6, phastCons 1
Regional constraint	o/e 0.90	unconstrained · MANE · 15 kb · p 0.0071 · regional, not allelic
Overall
CADD	27.3	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.Ala247Val
Coding: c.740C>T
MANE Select: NM_004086
dbSNP: rs749516210
Type: single nucleotide variant
Location: chr14:30885400 (GRCh38)
Gene constraint: LOEUF 0.896 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 85.93 · 1 PDB
Residue 247: a UniProt-annotated variant site (in dfnb110); the vwfa 1 domain

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

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

COCH p.Ala247Gly Uncertain significance ★ ⚠ same residue
COCH p.Arg148Gln Uncertain significance ★★ ⚠ same condition
COCH p.Asn335Ser Uncertain significance ★★ ⚠ same condition
COCH p.Glu25Gln Uncertain significance ★★ ⚠ same condition
COCH p.Gly135Arg Uncertain significance ★★ ⚠ same condition
COCH p.Gly327Ser Uncertain significance ★★ ⚠ same condition
COCH p.Gly75Glu Uncertain significance ★★ ⚠ same condition
COCH p.Met194Ile Uncertain significance ★★ ⚠ 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-ala247val (accessed [today's date]).

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