Is CDH23 p.Val2274fs (c.6821_6822del) pathogenic?

CDH23 p.Val2274fs (c.68216822del) is classified Likely pathogenic in CDH23 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-07-10). Absent from gnomAD; Associated with Usher syndrome type 1.

What condition is associated with CDH23 p.Val2274fs (c.6821_6822del)?

CDH23 p.Val2274fs (c.6821_6822del) is associated with Usher syndrome type 1, pituitary adenoma 5, multiple types (ClinVar).

How common is CDH23 p.Val2274fs (c.6821_6822del) in the general population?

CDH23 p.Val2274fs (c.6821_6822del) is absent from gnomAD (gnomAD).

How is Usher syndrome inherited?

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

CDH23 p.Val2274fs

c.6821_6822del · rs2494395471 · VCV2680530

Likely pathogenic Multiple submitters

Classification

Likely pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

Consequence

frameshift

predicted LoF

gnomAD v4.1

Not reported

no gnomAD frequency available for this variant

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 49 of 70
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 11	GERP 1.9, phastCons 1

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

Population frequency

dbSNP / gnomAD

No gnomAD frequency available for this variant. This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: CDH23
Protein: p.Val2274fs
Coding: c.6821_6822del
MANE Select: NM_022124
dbSNP: rs2494395471
Type: Microsatellite
Location: chr10:71797209 (GRCh38)
Gene constraint: LOEUF 0.685 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Residue 2274: the cadherin 21 domain

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

Also linked: pituitary adenoma 5, multiple types

For Usher syndrome (Orphanet):

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

Similar variants

CDH23 p.Gln462fs Pathogenic/Likely pathogenic ★★ same condition
CDH23 p.Gly2156fs Pathogenic/Likely pathogenic ★★ same condition
CDH23 p.Phe2664del Pathogenic/Likely pathogenic ★★ same condition
CDH23 p.Ser3157fs Pathogenic/Likely pathogenic ★★ same condition
CDH23 p.Lys2775del Uncertain significance ★★ same condition
CDH23 p.Arg116fs Likely pathogenic ★ same condition
CDH23 p.Glu96fs Likely pathogenic ★ same condition
CDH23 p.Ser2155fs Likely 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-val2274fs (accessed [today's date]).

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