Is CDH23 p.Val1192Ile (c.3574G>A) pathogenic?

CDH23 p.Val1192Ile (c.3574G>A) is classified Conflicting classifications of pathogenicity in CDH23 (ClinVar, Conflicting submitters, 5 submitters; last evaluated 2026-02-04). AlphaMissense: likely benign (0.1123); Low-frequency (popmax 3.19%, afr); Associated with Usher syndrome type 1D.

What condition is associated with CDH23 p.Val1192Ile (c.3574G>A)?

CDH23 p.Val1192Ile (c.3574G>A) is associated with Usher syndrome type 1D, Usher syndrome type 1, autosomal recessive nonsyndromic hearing loss 12 (ClinVar).

How common is CDH23 p.Val1192Ile (c.3574G>A) in the general population?

CDH23 p.Val1192Ile (c.3574G>A) is low-frequency (popmax 3.19%, afr) (gnomAD).

What do computational predictors say about CDH23 p.Val1192Ile (c.3574G>A)?

AlphaMissense predicts likely benign (score 0.1123) — an in-silico prediction, not a clinical call.

CDH23 p.Val1192Ile

c.3574G>A · rs80028391 · VCV45923

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 5 submitters

AlphaMissense

likely benign

0.1123 · ACMG-weighted

gnomAD v4.1

Rare

low-frequency (popmax 3.19%, afr)

Missense predictors

0/2 damaging

AlphaMissense, REVEL

Conditions

Usher syndrome type 1D

Computational evidence

Protein change
AlphaMissense	0.1123	likely benign
REVEL	0.097	moderately benign-leaning
⇒ AlphaMissense and REVEL both call this tolerated.
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP 3.1	GERP 0.18, phastCons 1
Regional constraint	o/e 0.96	unconstrained · MANE · 359 kb · p 0.017 · regional, not allelic
Overall
CADD	19.81	PHRED · no single calibrated threshold — expert panels disagree

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 3.19% African / African-American · 2,392/75,024 alleles

Filtering AF 3.08% ClinGen BA1/BS1 input FAF95, joint · FAF99 3.04%

Overall 0.163% 2,634/1,612,846 alleles · low-frequency

Ancestry group	Frequency	1 in
African / African-Americangrpmax	3.19%	31
Remaining individualsnot grpmax-eligible	0.192%	520
Admixed American	0.122%	820
Middle Eastern	0.0825%	1,212
South Asian	0.0121%	8,257
Finnishnot grpmax-eligible	0.00313%	31,943
European (non-Finnish)	0.00263%	38,047

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: CDH23
Protein: p.Val1192Ile
Coding: c.3574G>A
MANE Select: NM_001164375 · reported on NM_022124
dbSNP: rs80028391
Type: single nucleotide variant
Location: chr10:71725515 (GRCh38)

Full CDH23 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Usher syndrome type 1D — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: Usher syndrome type 1 autosomal recessive nonsyndromic hearing loss 12

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/cdh23-p-val1192ile (accessed [today's date]).

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