Is CDH23 p.Arg2935Ter (c.8803C>T) pathogenic?

CDH23 p.Arg2935Ter (c.8803C>T) is classified Pathogenic in CDH23 (ClinVar, Multiple submitters, 7 submitters; last evaluated 2025-01-15). Very rare (popmax 0.00333%, amr); Associated with CDH23-related disorder.

What condition is associated with CDH23 p.Arg2935Ter (c.8803C>T)?

CDH23 p.Arg2935Ter (c.8803C>T) is associated with CDH23-related disorder, Usher syndrome type 1, Usher syndrome type 1D (ClinVar).

How common is CDH23 p.Arg2935Ter (c.8803C>T) in the general population?

CDH23 p.Arg2935Ter (c.8803C>T) is very rare (popmax 0.00333%, amr) (gnomAD).

CDH23 p.Arg2935Ter

c.8803C>T · rs1190307769 · VCV620124

Pathogenic Multiple submitters

Classification

Pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 7 submitters

Consequence

nonsense (stop-gain)

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.00333%, amr)

Conditions

CDH23-related disorder

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	nonsense (stop-gain)	predicted loss-of-function
NMD	predicted	premature termination codon in exon 61 of 70
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 4.1	GERP 0.32, phastCons 1
Overall
CADD	46.0	PHRED · no single calibrated threshold — expert panels disagree

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00333% Admixed American · 2/60,008 alleles

Filtering AF 0.000553% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000207%

Overall 0.00031% 5/1,613,156 alleles · very rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00333%	30,004
African / African-American	0.00267%	37,463
European (non-Finnish)	8.48e-05%	1,179,903

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.Arg2935Ter
Coding: c.8803C>T
MANE Select: NM_022124
dbSNP: rs1190307769
Type: single nucleotide variant
Location: chr10:71809900 (GRCh38)
Gene constraint: LOEUF 0.685 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Residue 2935: the cadherin 27 domain

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 pituitary adenoma 5, multiple types

Similar variants

CDH23 p.Arg2935Gln Uncertain significance ★★ ⚠ same residue
CDH23 p.Arg2935Gly 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

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-arg2935ter (accessed [today's date]).

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