Is CDH23 p.Thr861fs (c.2580dup) pathogenic?

CDH23 p.Thr861fs (c.2580dup) is classified Likely pathogenic in CDH23 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-01-09). Associated with autosomal recessive nonsyndromic hearing loss 12.

What condition is associated with CDH23 p.Thr861fs (c.2580dup)?

CDH23 p.Thr861fs (c.2580dup) is associated with autosomal recessive nonsyndromic hearing loss 12 (ClinVar).

CDH23 p.Thr861fs

c.2580dup · VCV3601205

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 23 of 70
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 12	GERP 2.5, phastCons 1

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

Variant & gene context

Gene: CDH23
Protein: p.Thr861fs
Coding: c.2580dup
MANE Select: NM_022124
Type: Duplication
Location: chr10:71702202 (GRCh38)
Gene constraint: LOEUF 0.685 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Residue 861: the cadherin 8 domain; a β-strand

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

Similar variants

CDH23 p.Glu1753Ter Pathogenic/Likely pathogenic ★★ same condition
CDH23 p.His1769fs Pathogenic/Likely pathogenic ★★ same condition
CDH23 p.Ser166fs Pathogenic/Likely pathogenic ★★ same condition
CDH23 p.Thr861Ala Uncertain significance ★★ ⚠ same residue
CDH23 p.Ala2797fs Pathogenic ★ same condition
CDH23 p.Asp1486fs Pathogenic ★ same condition
CDH23 p.Asp1747fs Likely pathogenic ★ same condition
CDH23 p.Gly2984fs 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-thr861fs (accessed [today's date]).

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