Is CDH23 p.Trp778fs (c.2332_2333del) pathogenic?

CDH23 p.Trp778fs (c.23322333del) is classified Likely pathogenic in CDH23 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-09-05). Associated with Usher syndrome type 1.

What condition is associated with CDH23 p.Trp778fs (c.2332_2333del)?

CDH23 p.Trp778fs (c.2332_2333del) is associated with Usher syndrome type 1 (ClinVar).

How is Usher syndrome inherited?

Typically Autosomal recessive (Orphanet). A genetic counselor can assess individual risk for a family.

CDH23 p.Trp778fs

c.2332_2333del · VCV4816072

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

Conditions

Usher syndrome type 1

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 22 of 70
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 0.82	GERP -2.3, phastCons 0.004

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

Variant & gene context

Gene: CDH23
Protein: p.Trp778fs
Coding: c.2332_2333del
MANE Select: NM_022124
Type: Deletion
Location: chr10:71695459 (GRCh38)
Gene constraint: LOEUF 0.685 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Residue 778: the cadherin 7 domain; a β-strand

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

Disease context

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

For Usher syndrome (Orphanet):

Inheritance: Autosomal recessive
Onset: Childhood, Infancy, Neonatal
Prevalence: 1-9 / 100 000 (Worldwide)

Similar variants

CDH23 c.336+1del Likely pathogenic ★★ same condition
CDH23 p.Ala2232_Val2233insTer Pathogenic/Likely pathogenic ★★ same condition
CDH23 p.Ala2309fs Pathogenic/Likely pathogenic ★★ same condition
CDH23 p.Arg2115fs Pathogenic/Likely pathogenic ★★ same condition
CDH23 p.Asn393fs Pathogenic/Likely pathogenic ★★ same condition
CDH23 p.Gly2150fs Pathogenic/Likely pathogenic ★★ same condition
CDH23 p.Ile2132fs Pathogenic ★★ same condition
CDH23 p.Ile311_Leu312insTer 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-trp778fs (accessed [today's date]).

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