Is COCH p.Gly205= (c.615C>T) pathogenic?

COCH p.Gly205= (c.615C>T) is classified Benign/Likely benign in COCH (ClinVar, Multiple submitters, 5 submitters; last evaluated 2024-06-25). Rare (popmax 0.378%, sas); Associated with autosomal dominant nonsyndromic hearing loss 9.

What condition is associated with COCH p.Gly205= (c.615C>T)?

COCH p.Gly205= (c.615C>T) is associated with autosomal dominant nonsyndromic hearing loss 9 (ClinVar).

How common is COCH p.Gly205= (c.615C>T) in the general population?

COCH p.Gly205= (c.615C>T) is rare (popmax 0.378%, sas) (gnomAD).

COCH p.Gly205=

c.615C>T · rs548387738 · VCV883531

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 5 submitters

gnomAD v4.1

Rare

rare (popmax 0.378%, sas)

Conditions

autosomal dominant nonsyndromic hearing loss 9

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.006	strongly benign-leaning
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -0.18	GERP -2.4, phastCons 0.24
Overall
CADD	8.787	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.378% South Asian · 344/91,052 alleles

Filtering AF 0.345% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.332%

Overall 0.025% 404/1,613,262 alleles · rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.378%	265
Middle Eastern	0.0495%	2,021
Remaining individualsnot grpmax-eligible	0.032%	3,125
Ashkenazi Jewishnot grpmax-eligible	0.00338%	29,606
European (non-Finnish)	0.00305%	32,763

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.Gly205=
Coding: c.615C>T
MANE Select: NM_004086
dbSNP: rs548387738
Type: single nucleotide variant
Location: chr14:30880720 (GRCh38)
Gene constraint: LOEUF 0.896 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 85.93 · 1 PDB
Residue 205: 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

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

Similar variants

COCH p.Gly205Val Uncertain significance ★★ same residue
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

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-gly205 (accessed [today's date]).

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