Is COCH p.Pro143= (c.429A>G) pathogenic?

COCH p.Pro143= (c.429A>G) is classified Benign in COCH (ClinVar, Expert panel, 6 submitters; last evaluated 2019-03-25). Rare (popmax 0.143%, afr); Associated with nonsyndromic genetic hearing loss.

What condition is associated with COCH p.Pro143= (c.429A>G)?

COCH p.Pro143= (c.429A>G) is associated with nonsyndromic genetic hearing loss, autosomal dominant nonsyndromic hearing loss 9 (ClinVar).

How common is COCH p.Pro143= (c.429A>G) in the general population?

COCH p.Pro143= (c.429A>G) is rare (popmax 0.143%, afr) (gnomAD).

How is Rare non-syndromic genetic deafness inherited?

Typically Autosomal dominant, Autosomal recessive (Orphanet). A genetic counselor can assess individual risk for a family.

COCH p.Pro143=

c.429A>G · rs147841606 · VCV227258

Benign Expert panel

Classification

Benign

ClinVar

Review

Expert panel ★★★☆

ClinVar · 6 submitters

gnomAD v4.1

Rare

rare (popmax 0.143%, afr)

Conditions

nonsyndromic genetic hearing loss

ClinGen expert panel — Hearing Loss VCEP

Benign for nonsyndromic genetic deafness. Applied ACMG criteria (verbatim):

BA1

Curation rationale (ClinGen, verbatim)

The filtering allele frequency (the lower threshold of the 95% CI of 44/24026) of the c.429A>G (p.Pro143=) variant in the COCH gene is 0.14% for African chromosomes by gnomAD, which is a high enough frequency to be classified as benign based on thresholds defined by the ClinGen Hearing Loss Expert Panel for autosomal dominant hearing loss variants (BA1).

ClinGen Evidence Repository → · reported verbatim, not re-tallied by Sugi Variant.

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.03	GERP 1.7, phastCons 0.001
Overall
CADD	9.178	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.143% African / African-American · 107/75,056 alleles

Filtering AF 0.121% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.112%

Overall 0.00929% 150/1,614,130 alleles · rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.143%	701
Admixed American	0.035%	2,858
Remaining individualsnot grpmax-eligible	0.0304%	3,289
South Asian	0.0011%	91,092
European (non-Finnish)	0.000169%	589,984

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.Pro143=
Coding: c.429A>G
MANE Select: NM_004086
dbSNP: rs147841606
Type: single nucleotide variant
Location: chr14:30879478 (GRCh38)
Gene constraint: LOEUF 0.896 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 85.93 · 1 PDB
Residue 143: a UniProt-annotated variant site (in dfnb110); the 'disordered' region

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

Disease context

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

Also linked: autosomal dominant nonsyndromic hearing loss 9

For Rare non-syndromic genetic deafness (Orphanet):

Inheritance: Autosomal dominant, Autosomal recessive, X-linked recessive
Onset: Infancy, Neonatal

Similar variants

COCH p.Pro143Leu 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.Arg98Ter Likely pathogenic ★★ same condition
COCH p.Cys542Phe 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-pro143 (accessed [today's date]).

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