Is CDH23 p.Trp22Ter (c.65G>A) pathogenic?

CDH23 p.Trp22Ter (c.65G>A) is classified Pathogenic in CDH23 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2024-12-06). Very rare (popmax 0.000518%, nfe); Associated with CDH23-related disorder.

What condition is associated with CDH23 p.Trp22Ter (c.65G>A)?

CDH23 p.Trp22Ter (c.65G>A) is associated with CDH23-related disorder, Usher syndrome (ClinVar).

How common is CDH23 p.Trp22Ter (c.65G>A) in the general population?

CDH23 p.Trp22Ter (c.65G>A) is very rare (popmax 0.000518%, nfe) (gnomAD).

CDH23 p.Trp22Ter

c.65G>A · rs1431027601 · VCV1071750

Pathogenic Multiple submitters

Classification

Pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

Consequence

nonsense (stop-gain)

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.000518%, nfe)

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 2 of 70
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 6.5	GERP 1.1, phastCons 1
Overall
CADD	44.0	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 0.000518% European (non-Finnish) · 6/1,157,408 alleles

Filtering AF 0.000186% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000123%

Overall 0.000382% 6/1,571,702 alleles · very rare

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.Trp22Ter
Coding: c.65G>A
MANE Select: NM_022124
dbSNP: rs1431027601
Type: single nucleotide variant
Location: chr10:71439896 (GRCh38)
Gene constraint: LOEUF 0.685 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)

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

Disease context

CDH23-related disorder

Also linked: Usher syndrome

Similar variants

CDH23 p.Asp127Gly Likely 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
CDH23 p.Arg3189Gln Uncertain significance ★★★ ⚠ same condition
CDH23 p.Arg3189Trp Uncertain significance ★★★ ⚠ same condition
CDH23 p.Pro2205Leu Uncertain significance ★★★ same condition
CDH23 p.Val1711Ile Likely benign ★★★ 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-trp22ter (accessed [today's date]).

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