Is CDH23 p.Arg1897Trp (c.5689C>T) pathogenic?

CDH23 p.Arg1897Trp (c.5689C>T) is classified Uncertain significance in CDH23 (ClinVar, Multiple submitters, 5 submitters; last evaluated 2022-12-15). AlphaMissense: likely benign (0.125); Very rare (popmax 0.0072%, nfe); Associated with autosomal recessive nonsyndromic hearing loss 12.

What condition is associated with CDH23 p.Arg1897Trp (c.5689C>T)?

CDH23 p.Arg1897Trp (c.5689C>T) is associated with autosomal recessive nonsyndromic hearing loss 12, Usher syndrome type 1, Usher syndrome type 1D (ClinVar).

How common is CDH23 p.Arg1897Trp (c.5689C>T) in the general population?

CDH23 p.Arg1897Trp (c.5689C>T) is very rare (popmax 0.0072%, nfe) (gnomAD).

What do computational predictors say about CDH23 p.Arg1897Trp (c.5689C>T)?

AlphaMissense predicts likely benign (score 0.125) — an in-silico prediction, not a clinical call.

CDH23 p.Arg1897Trp

c.5689C>T · rs750798211 · VCV879909

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 5 submitters

AlphaMissense

likely benign

0.125 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.0072%, nfe)

Conditions

autosomal recessive nonsyndromic hearing loss 12

Computational evidence

Protein change
AlphaMissense	0.125	likely benign
REVEL	0.64	indeterminate
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.23	GERP -0.67, phastCons 0.97
Regional constraint	o/e 0.96	unconstrained · MANE · 359 kb · p 0.017 · regional, not allelic
Overall
CADD	24.7	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 0.0072% European (non-Finnish) · 85/1,179,806 alleles

Filtering AF 0.00596% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00549%

Overall 0.00545% 88/1,613,840 alleles · very rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.0072%	13,880
South Asian	0.0022%	45,543
Remaining individualsnot grpmax-eligible	0.0016%	62,466

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.Arg1897Trp
Coding: c.5689C>T
MANE Select: NM_022124
dbSNP: rs750798211
Type: single nucleotide variant
Location: chr10:71785077 (GRCh38)
Gene constraint: LOEUF 0.685 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Residue 1897: the cadherin 18 domain

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

Disease context

autosomal recessive nonsyndromic hearing loss 12 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

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

Similar variants

CDH23 p.Arg1897Gln 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
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-arg1897trp (accessed [today's date]).

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