Is CDH23 p.Arg834Cys (c.2500C>T) pathogenic?

CDH23 p.Arg834Cys (c.2500C>T) is classified Uncertain significance in CDH23 (ClinVar, Multiple submitters, 4 submitters; last evaluated 2026-01-12). AlphaMissense: ambiguous (0.3642); Very rare (popmax 0.00636%, nfe); Associated with Usher syndrome type 1.

What condition is associated with CDH23 p.Arg834Cys (c.2500C>T)?

CDH23 p.Arg834Cys (c.2500C>T) is associated with Usher syndrome type 1 (ClinVar).

How common is CDH23 p.Arg834Cys (c.2500C>T) in the general population?

CDH23 p.Arg834Cys (c.2500C>T) is very rare (popmax 0.00636%, nfe) (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.Arg834Cys (c.2500C>T)?

AlphaMissense predicts ambiguous (score 0.3642) — an in-silico prediction, not a clinical call.

CDH23 p.Arg834Cys

c.2500C>T · rs372387390 · VCV179700

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

AlphaMissense

ambiguous

0.3642 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00636%, nfe)

Conditions

Usher syndrome type 1

Computational evidence

Protein change
AlphaMissense	0.3642	ambiguous
REVEL	0.354	indeterminate
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 4.8	GERP 2.5, phastCons 1
Regional constraint	o/e 0.96	unconstrained · MANE · 359 kb · p 0.017 · regional, not allelic
Overall
CADD	33.0	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 0.00636% European (non-Finnish) · 75/1,179,898 alleles

Filtering AF 0.00519% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00474%

Overall 0.0049% 79/1,613,856 alleles · very rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00636%	15,732
Remaining individualsnot grpmax-eligible	0.0016%	62,462
Finnishnot grpmax-eligible	0.00156%	63,986
African / African-American	0.00133%	74,926
South Asian	0.0011%	91,090

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.Arg834Cys
Coding: c.2500C>T
MANE Select: NM_022124
dbSNP: rs372387390
Type: single nucleotide variant
Location: chr10:71702124 (GRCh38)
Gene constraint: LOEUF 0.685 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Residue 834: the cadherin 8 domain; a β-strand

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

Disease context

Usher syndrome type 1 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Usher syndrome (Orphanet):

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

Similar variants

CDH23 p.Arg834His Uncertain significance ★★ same residue
CDH23 p.Arg834= 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.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-arg834cys (accessed [today's date]).

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