Is CDH23 p.Val3056fs (c.9167del) pathogenic?

CDH23 p.Val3056fs (c.9167del) is classified Pathogenic in CDH23 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-02-20). Very rare (popmax 8.48e-05%, nfe); Associated with Usher syndrome type 1.

What condition is associated with CDH23 p.Val3056fs (c.9167del)?

CDH23 p.Val3056fs (c.9167del) is associated with Usher syndrome type 1 (ClinVar).

How common is CDH23 p.Val3056fs (c.9167del) in the general population?

CDH23 p.Val3056fs (c.9167del) is very rare (popmax 8.48e-05%, nfe) (gnomAD).

How is Usher syndrome inherited?

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

CDH23 p.Val3056fs

c.9167del · rs2133001560 · VCV1073475

Pathogenic Multiple submitters

Classification

Pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 8.48e-05%, nfe)

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 63 of 70
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 0.15	GERP -0.69

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 8.48e-05% European (non-Finnish) · 1/1,179,902 alleles

Overall 6.84e-05% 1/1,461,690 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.Val3056fs
Coding: c.9167del
MANE Select: NM_022124
dbSNP: rs2133001560
Type: Deletion
Location: chr10:71811404 (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 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-val3056fs (accessed [today's date]).

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