Is CDH23 p.Arg301Trp (c.901C>T) pathogenic?

CDH23 p.Arg301Trp (c.901C>T) is classified Conflicting classifications of pathogenicity in CDH23 (ClinVar, Conflicting submitters, 7 submitters; last evaluated 2025-09-15). AlphaMissense: likely pathogenic (0.6347); Very rare (popmax 0.00364%, nfe); Associated with CDH23-related disorder.

What condition is associated with CDH23 p.Arg301Trp (c.901C>T)?

CDH23 p.Arg301Trp (c.901C>T) is associated with CDH23-related disorder, Usher syndrome type 1, Usher syndrome type 1D (ClinVar).

How common is CDH23 p.Arg301Trp (c.901C>T) in the general population?

CDH23 p.Arg301Trp (c.901C>T) is very rare (popmax 0.00364%, nfe) (gnomAD).

What do computational predictors say about CDH23 p.Arg301Trp (c.901C>T)?

AlphaMissense predicts likely pathogenic (score 0.6347) — an in-silico prediction, not a clinical call.

CDH23 p.Arg301Trp

c.901C>T · rs397517364 · VCV46066

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 7 submitters

AlphaMissense

likely pathogenic

0.6347 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00364%, nfe)

Conditions

CDH23-related disorder

Computational evidence

Protein change
AlphaMissense	0.6347	likely pathogenic
REVEL	0.53	indeterminate
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 4.7	GERP 0.27, phastCons 1
Regional constraint	o/e 0.96	unconstrained · MANE · 359 kb · p 0.017 · regional, not allelic
Overall
CADD	29.0	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 0.00364% European (non-Finnish) · 43/1,179,870 alleles

Filtering AF 0.00275% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00244%

Overall 0.00285% 46/1,613,864 alleles · very rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00364%	27,439
Remaining individualsnot grpmax-eligible	0.0032%	31,232
African / African-American	0.00133%	74,926

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.Arg301Trp
Coding: c.901C>T
MANE Select: NM_022124
dbSNP: rs397517364
Type: single nucleotide variant
Location: chr10:71615572 (GRCh38)
Gene constraint: LOEUF 0.685 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Residue 301: the cadherin 3 domain; a UniProt-annotated variant site (in dfnb12; uncertain significance)

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

Disease context

CDH23-related disorder

Also linked: Usher syndrome type 1 Usher syndrome type 1D

Similar variants

CDH23 p.Arg301Gln Uncertain significance ★★★ same residue
CDH23 p.Arg301= Likely benign ★ 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-arg301trp (accessed [today's date]).

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