Is CDH23 p.Pro2323fs (c.6968del) pathogenic?

CDH23 p.Pro2323fs (c.6968del) is classified Pathogenic/Likely pathogenic in CDH23 (ClinVar, Multiple submitters, 4 submitters; last evaluated 2024-03-27). Very rare (popmax 0.000254%, nfe); Associated with CDH23-related disorder.

What condition is associated with CDH23 p.Pro2323fs (c.6968del)?

CDH23 p.Pro2323fs (c.6968del) is associated with CDH23-related disorder, Usher syndrome type 1, pituitary adenoma 5, multiple types (ClinVar).

How common is CDH23 p.Pro2323fs (c.6968del) in the general population?

CDH23 p.Pro2323fs (c.6968del) is very rare (popmax 0.000254%, nfe) (gnomAD).

CDH23 p.Pro2323fs

c.6968del · rs397517350 · VCV46023

Pathogenic/Likely pathogenic Multiple submitters

Classification

Pathogenic/Likely pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.000254%, nfe)

Conditions

CDH23-related disorder

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function
NMD	predicted	premature termination codon in exon 50 of 70
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 11	GERP 1.9, phastCons 1
Overall
CADD	32.0	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 0.000254% European (non-Finnish) · 3/1,179,862 alleles

Filtering AF 6.8e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.9e-05%

Overall 0.000186% 3/1,613,840 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.Pro2323fs
Coding: c.6968del
MANE Select: NM_022124
dbSNP: rs397517350
Type: Deletion
Location: chr10:71798490 (GRCh38)
Gene constraint: LOEUF 0.685 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Residue 2323: the cadherin 22 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 pituitary adenoma 5, multiple types

Similar variants

CDH23 c.1143_1176del Pathogenic/Likely pathogenic ★★ same condition
CDH23 c.336+1del Likely pathogenic ★★ same condition
CDH23 c.9280_9286del Pathogenic/Likely pathogenic ★★ same condition
CDH23 p.Ala2232_Val2233insTer Pathogenic/Likely pathogenic ★★ same condition
CDH23 p.Ala2309fs Pathogenic/Likely pathogenic ★★ same condition
CDH23 p.Ala2685fs Pathogenic ★★ same condition
CDH23 p.Arg2115fs Pathogenic/Likely pathogenic ★★ same condition
CDH23 p.Asn1889fs Likely pathogenic ★★ 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-pro2323fs (accessed [today's date]).

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