Is CDH23 p.Phe284fs (c.849del) pathogenic?

CDH23 p.Phe284fs (c.849del) is classified Pathogenic in CDH23 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-08-05). Very rare (popmax 0.00017%, nfe).

How common is CDH23 p.Phe284fs (c.849del) in the general population?

CDH23 p.Phe284fs (c.849del) is very rare (popmax 0.00017%, nfe) (gnomAD).

CDH23 p.Phe284fs

c.849del · rs1861132418 · VCV866055

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.00017%, nfe)

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 10 of 70
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 7.7	GERP 2.1, phastCons 1

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00017% European (non-Finnish) · 2/1,177,898 alleles

Filtering AF 2.8e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.1e-05%

Overall 0.000137% 2/1,458,888 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.Phe284fs
Coding: c.849del
MANE Select: NM_022124
dbSNP: rs1861132418
Type: Deletion
Location: chr10:71615520 (GRCh38)
Gene constraint: LOEUF 0.685 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Residue 284: the cadherin 3 domain

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

Similar variants

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
CDH23 p.Asn1889fs 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-phe284fs (accessed [today's date]).

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