Is COCH p.Pro51= (c.153A>C) pathogenic?

COCH p.Pro51= (c.153A>C) is classified Conflicting classifications of pathogenicity in COCH (ClinVar, Conflicting submitters, 5 submitters; last evaluated 2025-07-06). Rare (popmax 0.213%, afr).

How common is COCH p.Pro51= (c.153A>C) in the general population?

COCH p.Pro51= (c.153A>C) is rare (popmax 0.213%, afr) (gnomAD).

COCH p.Pro51=

c.153A>C · rs573330522 · VCV287013

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 5 submitters

gnomAD v4.1

Rare

rare (popmax 0.213%, afr)

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 0.037	GERP -3.3, phastCons 0.067
Overall
CADD	7.969	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.213% African / African-American · 160/75,058 alleles

Filtering AF 0.186% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.176%

Overall 0.011% 177/1,614,210 alleles · rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.213%	469
Remaining individualsnot grpmax-eligible	0.0208%	4,808
Admixed American	0.00666%	15,008

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.Pro51=
Coding: c.153A>C
dbSNP: rs573330522
Type: single nucleotide variant
Location: chr14:30877642 (GRCh38)

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

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-pro51 (accessed [today's date]).

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