Is CDH23 p.Val1711Ala (c.5132T>C) pathogenic?

CDH23 p.Val1711Ala (c.5132T>C) is classified Uncertain significance in CDH23 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2024-01-17). AlphaMissense: likely pathogenic (0.6432); Very rare (popmax 0.00439%, sas); Associated with Usher syndrome type 1.

What condition is associated with CDH23 p.Val1711Ala (c.5132T>C)?

CDH23 p.Val1711Ala (c.5132T>C) is associated with Usher syndrome type 1 (ClinVar).

How common is CDH23 p.Val1711Ala (c.5132T>C) in the general population?

CDH23 p.Val1711Ala (c.5132T>C) is very rare (popmax 0.00439%, sas) (gnomAD).

How is Usher syndrome inherited?

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

What do computational predictors say about CDH23 p.Val1711Ala (c.5132T>C)?

AlphaMissense predicts likely pathogenic (score 0.6432) — an in-silico prediction, not a clinical call.

CDH23 p.Val1711Ala

c.5132T>C · rs762613557 · VCV970085

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

AlphaMissense

likely pathogenic

0.6432 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00439%, sas)

Conditions

Usher syndrome type 1

Computational evidence

Protein change
AlphaMissense	0.6432	likely pathogenic
REVEL	0.451	indeterminate
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 6.2	GERP 1.7, phastCons 1
Regional constraint	o/e 0.96	unconstrained · MANE · 359 kb · p 0.017 · regional, not allelic
Overall
CADD	26.3	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 0.00439% South Asian · 4/91,070 alleles

Filtering AF 0.00143% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000891%

Overall 0.00155% 25/1,613,630 alleles · very rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.00439%	22,767
Admixed American	0.00167%	59,942
European (non-Finnish)	0.00161%	62,098
Remaining individualsnot grpmax-eligible	0.0016%	62,458

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.Val1711Ala
Coding: c.5132T>C
MANE Select: NM_022124
dbSNP: rs762613557
Type: single nucleotide variant
Location: chr10:71778253 (GRCh38)
Gene constraint: LOEUF 0.685 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Residue 1711: a UniProt-annotated variant site (in); the cadherin 16 domain

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

Disease context

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

For Usher syndrome (Orphanet):

Inheritance: Autosomal recessive
Onset: Childhood, Infancy, Neonatal
Prevalence: 1-9 / 100 000 (Worldwide)

Similar variants

CDH23 p.Val1711Ile Likely benign ★★★ same residue
CDH23 p.Val1711Phe Uncertain significance ★ same residue
CDH23 p.Arg2029Trp Pathogenic ★★★ ⚠ same condition
CDH23 p.Asp127Gly Likely pathogenic ★★★ same condition
CDH23 p.Glu956Lys Pathogenic ★★★ same condition
CDH23 p.Pro240Leu Pathogenic ★★★ same condition
CDH23 c.1515-12G>A Uncertain significance ★★★ same condition
CDH23 p.Arg301Gln Uncertain significance ★★★ 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/cdh23-p-val1711ala (accessed [today's date]).

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