Is CDH23 p.Asp1059Val (c.3176A>T) pathogenic?

CDH23 p.Asp1059Val (c.3176A>T) is classified Likely pathogenic in CDH23 (ClinVar, Single submitter, 1 submitter; last evaluated 2021-07-08). AlphaMissense: likely pathogenic (0.9664); Absent from gnomAD v4.1; Associated with Childhood onset hearing loss.

What condition is associated with CDH23 p.Asp1059Val (c.3176A>T)?

CDH23 p.Asp1059Val (c.3176A>T) is associated with Childhood onset hearing loss (ClinVar).

How common is CDH23 p.Asp1059Val (c.3176A>T) in the general population?

CDH23 p.Asp1059Val (c.3176A>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about CDH23 p.Asp1059Val (c.3176A>T)?

AlphaMissense predicts likely pathogenic (score 0.9664) — an in-silico prediction, not a clinical call.

CDH23 p.Asp1059Val

c.3176A>T · rs1865887896 · VCV1027558

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9664 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

2/2 damaging

AlphaMissense, REVEL

Conditions

Childhood onset hearing loss

Computational evidence

Protein change
AlphaMissense	0.9664	likely pathogenic ✓ concordant with ClinVar · top 9% in CDH23
REVEL	0.965	strongly pathogenic-leaning
⇒ AlphaMissense and REVEL both call this damaging.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 11	GERP 2.3, phastCons 1
Regional constraint	o/e 0.96	unconstrained · MANE · 359 kb · p 0.017 · regional, not allelic
Overall
CADD	29.0	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: CDH23
Protein: p.Asp1059Val
Coding: c.3176A>T
MANE Select: NM_022124
dbSNP: rs1865887896
Type: single nucleotide variant
Location: chr10:71709167 (GRCh38)
Gene constraint: LOEUF 0.685 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Residue 1059: the cadherin 10 domain

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

Disease context

Childhood onset hearing loss

Similar variants

CDH23 p.Asp1059His Uncertain significance ★ ⚠ same residue
CDH23 p.Asp1059= Likely benign ★ same residue
CDH23 c.1752+1G>A Likely pathogenic ★★ same condition
CDH23 c.2176+1G>A Likely pathogenic ★★ same condition
CDH23 c.2177-2A>G Pathogenic/Likely pathogenic ★★ same condition
CDH23 c.2289+1G>A Pathogenic ★★ same condition
CDH23 c.289-1G>A Likely pathogenic ★★ same condition
CDH23 c.336+1G>A 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-asp1059val (accessed [today's date]).

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