Is CDH23 p.Thr992fs (c.2974del) pathogenic?

CDH23 p.Thr992fs (c.2974del) is classified Likely pathogenic in CDH23 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-01-17). Associated with autosomal recessive nonsyndromic hearing loss 12.

What condition is associated with CDH23 p.Thr992fs (c.2974del)?

CDH23 p.Thr992fs (c.2974del) is associated with autosomal recessive nonsyndromic hearing loss 12, Usher syndrome type 1D (ClinVar).

CDH23 p.Thr992fs

c.2974del · VCV4845709

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

Conditions

autosomal recessive nonsyndromic hearing loss 12

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 26 of 70
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 7.5	GERP -1.1, phastCons 1

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

Variant & gene context

Gene: CDH23
Protein: p.Thr992fs
Coding: c.2974del
MANE Select: NM_022124
Type: Deletion
Location: chr10:71706917 (GRCh38)
Gene constraint: LOEUF 0.685 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Residue 992: the cadherin 9 domain

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

Disease context

autosomal recessive nonsyndromic hearing loss 12 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: Usher syndrome type 1D

Similar variants

CDH23 c.1143_1176del Pathogenic/Likely pathogenic ★★ same condition
CDH23 c.9280_9286del Pathogenic/Likely pathogenic ★★ same condition
CDH23 p.Ala2232_Val2233insTer Pathogenic/Likely pathogenic ★★ same condition
CDH23 p.Asp2716fs Likely pathogenic ★★ same condition
CDH23 p.Ile2132fs Pathogenic ★★ same condition
CDH23 p.Leu1026fs Pathogenic ★★ same condition
CDH23 p.Leu2785fs Likely pathogenic ★★ same condition
CDH23 p.Leu3085fs Pathogenic/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-thr992fs (accessed [today's date]).

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