Is CDH23 p.Asp1648fs (c.4942_4943del) pathogenic?

CDH23 p.Asp1648fs (c.49424943del) is classified Pathogenic in CDH23 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-04-08). Very rare (popmax 0.00167%, amr).

How common is CDH23 p.Asp1648fs (c.4942_4943del) in the general population?

CDH23 p.Asp1648fs (c.4942_4943del) is very rare (popmax 0.00167%, amr) (gnomAD).

CDH23 p.Asp1648fs

c.4942_4943del · rs1564788732 · VCV1397503

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.00167%, amr)

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 39 of 70
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 6	GERP 1.9, phastCons 1

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00167% Admixed American · 1/60,010 alleles

Overall 0.000137% 2/1,461,608 alleles · very rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00167%	60,010
Remaining individualsnot grpmax-eligible	0.0016%	62,480

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.Asp1648fs
Coding: c.4942_4943del
MANE Select: NM_022124
dbSNP: rs1564788732
Type: Deletion
Location: chr10:71777775 (GRCh38)
Gene constraint: LOEUF 0.685 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Residue 1648: the cadherin 16 domain

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

Similar variants

CDH23 p.Asp1648= Likely benign ★ same residue
CDH23 c.1143_1176del Pathogenic/Likely pathogenic ★★ same type
CDH23 c.336+1del Likely pathogenic ★★ same type
CDH23 c.9280_9286del Pathogenic/Likely pathogenic ★★ same type
CDH23 p.Ala2232_Val2233insTer Pathogenic/Likely pathogenic ★★ same type
CDH23 p.Ala2309fs Pathogenic/Likely pathogenic ★★ same type
CDH23 p.Ala2685fs Pathogenic ★★ same type
CDH23 p.Arg2115fs Pathogenic/Likely pathogenic ★★ same type

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-asp1648fs (accessed [today's date]).

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