Is CDH23 p.Phe3083fs (c.9246_9247del) pathogenic?

CDH23 p.Phe3083fs (c.92469247del) is classified Pathogenic/Likely pathogenic in CDH23 (ClinVar, Multiple submitters, 4 submitters; last evaluated 2023-04-29). Very rare (popmax 0.00223%, eas); Associated with Usher syndrome type 1D.

What condition is associated with CDH23 p.Phe3083fs (c.9246_9247del)?

CDH23 p.Phe3083fs (c.9246_9247del) is associated with Usher syndrome type 1D, inherited retinal dystrophy (ClinVar).

How common is CDH23 p.Phe3083fs (c.9246_9247del) in the general population?

CDH23 p.Phe3083fs (c.9246_9247del) is very rare (popmax 0.00223%, eas) (gnomAD).

CDH23 p.Phe3083fs

c.9246_9247del · rs1841926049 · VCV1805315

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 0.00223%, eas)

Conditions

Usher syndrome type 1D

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 64 of 70
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 9.8	GERP 1.7, phastCons 1

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00223% East Asian · 1/44,868 alleles

Overall 6.84e-05% 1/1,461,686 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.Phe3083fs
Coding: c.9246_9247del
MANE Select: NM_022124
dbSNP: rs1841926049
Type: Microsatellite
Location: chr10:71811556 (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

Usher syndrome type 1D — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: inherited retinal dystrophy

Similar variants

CDH23 p.Phe2664del Pathogenic/Likely pathogenic ★★ same condition
CDH23 p.Phe3083Ile Uncertain significance ★★ ⚠ same residue
CDH23 c.9278_9278+3del Pathogenic ★ same condition
CDH23 p.Asn3197del Uncertain significance ★ same condition
CDH23 p.Phe3083Ser Uncertain significance ★ same residue
CDH23 p.Tyr1566del Conflicting classifications of pathogenicity ★ same condition
CDH23 p.Asn2399del Likely pathogenic same condition
CDH23 p.Arg2029Trp 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-phe3083fs (accessed [today's date]).

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