Is CDH23 p.Phe995fs (c.2984del) pathogenic?

CDH23 p.Phe995fs (c.2984del) is classified Pathogenic/Likely pathogenic in CDH23 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2022-02-01). Very rare (popmax 8.5e-05%, nfe); Associated with CDH23-related disorder.

What condition is associated with CDH23 p.Phe995fs (c.2984del)?

CDH23 p.Phe995fs (c.2984del) is associated with CDH23-related disorder (ClinVar).

How common is CDH23 p.Phe995fs (c.2984del) in the general population?

CDH23 p.Phe995fs (c.2984del) is very rare (popmax 8.5e-05%, nfe) (gnomAD).

CDH23 p.Phe995fs

c.2984del · rs1554858698 · VCV503854

Pathogenic/Likely pathogenic Multiple submitters

Classification

Pathogenic/Likely pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 8.5e-05%, 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 26 of 70
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 2.2	GERP 0.38, phastCons 1

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 8.5e-05% European (non-Finnish) · 1/1,176,322 alleles

Overall 6.23e-05% 1/1,605,276 alleles · very rare exomes 1/1,452,918 · genomes 0/152,358 · joint denominator

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.Phe995fs
Coding: c.2984del
MANE Select: NM_022124
dbSNP: rs1554858698
Type: Deletion
Location: chr10:71706926 (GRCh38)
Gene constraint: LOEUF 0.685 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Residue 995: the cadherin 9 domain

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

Disease context

CDH23-related disorder

Similar variants

CDH23 p.Asn1889fs Likely pathogenic ★★ same condition
CDH23 p.Ile2132fs Pathogenic ★★ same condition
CDH23 p.Ile3210fs Pathogenic/Likely pathogenic ★★ same condition
CDH23 p.Phe2577fs Pathogenic/Likely pathogenic ★★ same condition
CDH23 p.Pro2323fs Pathogenic/Likely pathogenic ★★ same condition
CDH23 p.Pro650fs Pathogenic/Likely pathogenic ★★ same condition
CDH23 p.Thr1587fs Pathogenic ★★ same condition
CDH23 p.Thr2052fs Pathogenic/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-phe995fs (accessed [today's date]).

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