Is CDH23 p.Asp228Val (c.683A>T) pathogenic?

CDH23 p.Asp228Val (c.683A>T) is classified Likely pathogenic in CDH23 (ClinVar, Single submitter, 2 submitters; last evaluated 2020-08-01). AlphaMissense: likely pathogenic (0.9657); Absent from gnomAD v4.1; Associated with autosomal recessive nonsyndromic hearing loss 12.

What condition is associated with CDH23 p.Asp228Val (c.683A>T)?

CDH23 p.Asp228Val (c.683A>T) is associated with autosomal recessive nonsyndromic hearing loss 12 (ClinVar).

How common is CDH23 p.Asp228Val (c.683A>T) in the general population?

CDH23 p.Asp228Val (c.683A>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about CDH23 p.Asp228Val (c.683A>T)?

AlphaMissense predicts likely pathogenic (score 0.9657) — an in-silico prediction, not a clinical call.

CDH23 p.Asp228Val

c.683A>T · rs1060499788 · VCV402247

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 2 submitters

AlphaMissense

likely pathogenic

0.9657 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Conditions

autosomal recessive nonsyndromic hearing loss 12

Computational evidence

Protein change
AlphaMissense	0.9657	likely pathogenic ✓ concordant with ClinVar · top 9% in CDH23
REVEL	0.613	indeterminate
SaProt	—	not scored · why
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 11	GERP 1.9, phastCons 1
Regional constraint	o/e 0.96	unconstrained · MANE · 359 kb · p 0.017 · regional, not allelic
Overall
CADD	25.3	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL is an independent agreement signal.

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.Asp228Val
Coding: c.683A>T
MANE Select: NM_022124
dbSNP: rs1060499788
Type: single nucleotide variant
Location: chr10:71570848 (GRCh38)
Gene constraint: LOEUF 0.685 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Residue 228: the cadherin 2 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

Similar variants

CDH23 p.Asp228= Likely benign ★ same residue
CDH23 p.Arg2029Trp Pathogenic ★★★ ⚠ same condition
CDH23 p.Asp127Gly Likely pathogenic ★★★ same condition
CDH23 p.Glu956Lys Pathogenic ★★★ same condition
CDH23 p.Pro240Leu Pathogenic ★★★ same condition
CDH23 p.Ala3190Val Uncertain significance ★★★ same condition
CDH23 p.Arg301Gln Uncertain significance ★★★ same condition
CDH23 p.Arg3189Trp Uncertain significance ★★★ ⚠ 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-asp228val (accessed [today's date]).

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