Is CDH23 p.Arg724Pro (c.2171G>C) pathogenic?

CDH23 p.Arg724Pro (c.2171G>C) is classified Uncertain significance in CDH23 (ClinVar, Multiple submitters, 4 submitters; last evaluated 2026-02-01). AlphaMissense: likely pathogenic (0.9351); Very rare (popmax 0.00673%, afr); Associated with Usher syndrome type 1D.

What condition is associated with CDH23 p.Arg724Pro (c.2171G>C)?

CDH23 p.Arg724Pro (c.2171G>C) is associated with Usher syndrome type 1D (ClinVar).

How common is CDH23 p.Arg724Pro (c.2171G>C) in the general population?

CDH23 p.Arg724Pro (c.2171G>C) is very rare (popmax 0.00673%, afr) (gnomAD).

What do computational predictors say about CDH23 p.Arg724Pro (c.2171G>C)?

AlphaMissense predicts likely pathogenic (score 0.9351) — an in-silico prediction, not a clinical call.

CDH23 p.Arg724Pro

c.2171G>C · rs374955091 · VCV1310876

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

AlphaMissense

likely pathogenic

0.9351 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00673%, afr)

Missense predictors

2/2 damaging

AlphaMissense, REVEL

Conditions

Usher syndrome type 1D

Computational evidence

Protein change
AlphaMissense	0.9351	likely pathogenic
REVEL	0.712	pathogenic-leaning
⇒ AlphaMissense and REVEL both call this damaging.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 2.3, phastCons 1

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00673% African / African-American · 5/74,294 alleles

Filtering AF 0.00257% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00163%

Overall 0.000378% 6/1,587,934 alleles · very rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00673%	14,859
European (non-Finnish)	8.58e-05%	1,165,897

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.Arg724Pro
Coding: c.2171G>C
MANE Select: NM_022124
dbSNP: rs374955091
Type: single nucleotide variant
Location: chr10:71690579 (GRCh38)
Gene constraint: LOEUF 0.685 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Residue 724: the cadherin 7 domain; a turn

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

Similar variants

CDH23 p.Arg724His Conflicting classifications of pathogenicity ★ same residue
CDH23 p.Arg724Gly Uncertain significance same residue
CDH23 p.Arg2029Trp 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.Arg3189Trp 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-arg724pro (accessed [today's date]).

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