Is COCH p.Thr36= (c.108C>T) pathogenic?

COCH p.Thr36= (c.108C>T) is classified Conflicting classifications of pathogenicity in COCH (ClinVar, Conflicting submitters, 3 submitters; last evaluated 2025-07-27). Very rare (popmax 0.00935%, afr); Associated with autosomal dominant nonsyndromic hearing loss 9.

What condition is associated with COCH p.Thr36= (c.108C>T)?

COCH p.Thr36= (c.108C>T) is associated with autosomal dominant nonsyndromic hearing loss 9 (ClinVar).

How common is COCH p.Thr36= (c.108C>T) in the general population?

COCH p.Thr36= (c.108C>T) is very rare (popmax 0.00935%, afr) (gnomAD).

COCH p.Thr36=

c.108C>T · rs372237012 · VCV882736

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 3 submitters

gnomAD v4.1

Rare

very rare (popmax 0.00935%, afr)

Conditions

autosomal dominant nonsyndromic hearing loss 9

⚠ Built without this gene's context — gene constraint and dosage, protein structure, pathways, panels and related-variant links were not looked up for this page. why

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP -0.2	GERP -1.3, phastCons 0.24
Overall
CADD	9.772	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00935% African / African-American · 7/74,904 alleles

Filtering AF 0.00437% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00309%

Overall 0.00112% 18/1,614,050 alleles · very rare exomes 17/1,461,876 · genomes 1/152,174 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00935%	10,701
Remaining individualsnot grpmax-eligible	0.0064%	15,623
European (non-Finnish)	0.000593%	168,577

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.Thr36=
Coding: c.108C>T
MANE Select: NM_004086
dbSNP: rs372237012
Type: single nucleotide variant
Location: chr14:30877597 (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-thr36 (accessed [today's date]).

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