Is CDH23 p.Val1711Ile (c.5131G>A) pathogenic?

CDH23 p.Val1711Ile (c.5131G>A) is classified Likely benign in CDH23 (ClinVar, Expert panel, 7 submitters; last evaluated 2019-10-29). AlphaMissense: likely benign (0.0775); Rare (popmax 0.183%, eas); Associated with Usher syndrome.

What condition is associated with CDH23 p.Val1711Ile (c.5131G>A)?

CDH23 p.Val1711Ile (c.5131G>A) is associated with Usher syndrome, Usher syndrome type 1D, autosomal recessive nonsyndromic hearing loss 12 (ClinVar).

How common is CDH23 p.Val1711Ile (c.5131G>A) in the general population?

CDH23 p.Val1711Ile (c.5131G>A) is rare (popmax 0.183%, eas) (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.Val1711Ile (c.5131G>A)?

AlphaMissense predicts likely benign (score 0.0775) — an in-silico prediction, not a clinical call.

CDH23 p.Val1711Ile

c.5131G>A · rs181611778 · VCV197422

Likely benign Expert panel

Classification

Likely benign

ClinVar

Review

Expert panel ★★★☆

ClinVar · 7 submitters

AlphaMissense

likely benign

0.0775 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.183%, eas)

Missense predictors

0/2 damaging

AlphaMissense, REVEL

Conditions

Usher syndrome

ClinGen expert panel — Hearing Loss VCEP

Likely Benign for Usher syndrome. Applied ACMG criteria (verbatim):

BS1 BP4

Curation rationale (ClinGen, verbatim)

The c.5131 (p.Val1711Ile) variant has been identified in 0.3% (51/19534 CI 95%) of East Asian alleles in gnomAD (BS1). This variant was observed in 1 patient with Usher syndrome, without a second variant in CDH23 (PMID: 25333064). Computational prediction analysis using the metapredictor tool REVEL produced a score of .17; this combined with the presence of the isoleucine amino acid at position 1711 in 5 organisms including 3 mammals in UCSC suggests that the variant may not impact the protein (BP4). In summary, this variant meets criteria to be classified as likely benign. ACMG/AMP criteria applied, as specified by the Hearing Loss Expert Panel: BS1, BP4.

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

Computational evidence

Protein change
AlphaMissense	0.0775	likely benign
REVEL	0.17	moderately benign-leaning
⇒ AlphaMissense and REVEL both call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 2.5	GERP 0.65, phastCons 1
Regional constraint	o/e 0.96	unconstrained · MANE · 359 kb · p 0.017 · regional, not allelic
Overall
CADD	20.8	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 0.183% East Asian · 82/44,886 alleles

Filtering AF 0.151% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.139%

Overall 0.0151% 244/1,613,738 alleles · rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.183%	547
South Asian	0.034%	2,938
Middle Eastern	0.0165%	6,062
Remaining individualsnot grpmax-eligible	0.0128%	7,810
European (non-Finnish)	0.01%	9,998
Ashkenazi Jewishnot grpmax-eligible	0.00676%	14,802
Admixed American	0.00333%	29,995

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.Val1711Ile
Coding: c.5131G>A
MANE Select: NM_022124
dbSNP: rs181611778
Type: single nucleotide variant
Location: chr10:71778252 (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 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: Usher syndrome type 1D autosomal recessive nonsyndromic hearing loss 12 pituitary adenoma 5, multiple types

For Usher syndrome (Orphanet):

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

Similar variants

CDH23 p.Val1711Ala Uncertain significance ★★ 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.Ala3190Val 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-val1711ile (accessed [today's date]).

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