Is CDH23 p.Val1908Ile (c.5722G>A) pathogenic?

CDH23 p.Val1908Ile (c.5722G>A) is classified Conflicting classifications of pathogenicity in CDH23 (ClinVar, Conflicting submitters, 6 submitters; last evaluated 2026-01-14). AlphaMissense: likely benign (0.0566); Rare (popmax 0.451%, eas); Associated with Usher syndrome type 1D.

What condition is associated with CDH23 p.Val1908Ile (c.5722G>A)?

CDH23 p.Val1908Ile (c.5722G>A) is associated with Usher syndrome type 1D, Usher syndrome type 1, autosomal recessive nonsyndromic hearing loss 12 (ClinVar).

How common is CDH23 p.Val1908Ile (c.5722G>A) in the general population?

CDH23 p.Val1908Ile (c.5722G>A) is rare (popmax 0.451%, eas) (gnomAD).

What do computational predictors say about CDH23 p.Val1908Ile (c.5722G>A)?

AlphaMissense predicts likely benign (score 0.0566) — an in-silico prediction, not a clinical call.

CDH23 p.Val1908Ile

c.5722G>A · rs368828743 · VCV197506

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 6 submitters

AlphaMissense

likely benign

0.0566 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.451%, eas)

Missense predictors

0/2 damaging

AlphaMissense, REVEL

Conditions

Usher syndrome type 1D

Computational evidence

Protein change
AlphaMissense	0.0566	likely benign
REVEL	0.094	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 0.16	GERP -0.47, phastCons 0.001
Regional constraint	o/e 0.96	unconstrained · MANE · 359 kb · p 0.017 · regional, not allelic
Overall
CADD	13.31	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 0.451% East Asian · 199/44,078 alleles

Filtering AF 0.4% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.38%

Overall 0.0142% 226/1,596,564 alleles · rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.451%	221
Remaining individualsnot grpmax-eligible	0.0194%	5,158
Middle Eastern	0.0166%	6,042
South Asian	0.00683%	14,649
African / African-American	0.00402%	24,881
European (non-Finnish)	0.000427%	234,162

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.Val1908Ile
Coding: c.5722G>A
MANE Select: NM_022124
dbSNP: rs368828743
Type: single nucleotide variant
Location: chr10:71785640 (GRCh38)
Gene constraint: LOEUF 0.685 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Residue 1908: a UniProt-annotated variant site (in); the cadherin 18 domain

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

Similar variants

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
CDH23 p.Arg301Gln Uncertain significance ★★★ same condition
CDH23 p.Arg3189Gln 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-val1908ile (accessed [today's date]).

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