Is COCH p.Asp507Glu (c.1521T>A) pathogenic?

COCH p.Asp507Glu (c.1521T>A) is classified Uncertain significance in COCH (ClinVar, Single submitter, 1 submitter; last evaluated 2025-10-08). AlphaMissense: likely benign (0.0751); Ultra-rare (popmax 0.0736%, sas); Associated with Inborn genetic diseases.

What condition is associated with COCH p.Asp507Glu (c.1521T>A)?

COCH p.Asp507Glu (c.1521T>A) is associated with Inborn genetic diseases (ClinVar).

How common is COCH p.Asp507Glu (c.1521T>A) in the general population?

COCH p.Asp507Glu (c.1521T>A) is ultra-rare (popmax 0.0736%, sas) (gnomAD).

What do computational predictors say about COCH p.Asp507Glu (c.1521T>A)?

AlphaMissense predicts likely benign (score 0.0751) — an in-silico prediction, not a clinical call.

COCH p.Asp507Glu

c.1521T>A · VCV4616080

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0751 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0736%, sas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.0751	likely benign
REVEL	0.199	benign-leaning
SaProt	LLR -6.12	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.97	GERP 1.3, phastCons 1
Regional constraint	o/e 0.90	unconstrained · MANE · 15 kb · p 0.0071 · regional, not allelic
Overall
CADD	16.1	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0736% South Asian · 67/91,088 alleles

Filtering AF 0.0593% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0542%

Overall 0.00421% 68/1,614,118 alleles · ultra-rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0736%	1,360
Remaining individualsnot grpmax-eligible	0.0016%	62,506

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.Asp507Glu
Coding: c.1521T>A
MANE Select: NM_004086
Type: single nucleotide variant
Location: chr14:30889659 (GRCh38)
Gene constraint: LOEUF 0.896 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 85.93 · 1 PDB
Residue 507: a UniProt-annotated variant site (in dfnb110); the vwfa 2 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.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
COCH p.Phe255Ser 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-asp507glu (accessed [today's date]).

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