Is CDH23 p.Asp486Val (c.1457A>T) pathogenic?

CDH23 p.Asp486Val (c.1457A>T) is classified Uncertain significance in CDH23 (ClinVar, Single submitter, 1 submitter; last evaluated 2021-02-19). AlphaMissense: likely pathogenic (0.9872); Absent from gnomAD v4.1.

How common is CDH23 p.Asp486Val (c.1457A>T) in the general population?

CDH23 p.Asp486Val (c.1457A>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about CDH23 p.Asp486Val (c.1457A>T)?

AlphaMissense predicts likely pathogenic (score 0.9872) — an in-silico prediction, not a clinical call.

CDH23 p.Asp486Val

c.1457A>T · VCV4907813

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9872 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

2/2 damaging

AlphaMissense, REVEL

Computational evidence

Protein change
AlphaMissense	0.9872	likely pathogenic · top 4% in CDH23
REVEL	0.942	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 1.8, phastCons 1
Regional constraint	o/e 0.96	unconstrained · MANE · 359 kb · p 0.017 · regional, not allelic
Overall
CADD	25.5	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — a triage signal, not a reclassification

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.Asp486Val
Coding: c.1457A>T
MANE Select: NM_022124
Type: single nucleotide variant
Location: chr10:71675119 (GRCh38)
Gene constraint: LOEUF 0.685 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Residue 486: the cadherin 5 domain

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

Similar variants

CDH23 p.Asp486Glu Uncertain significance ★★ ⚠ same residue
CDH23 p.Asp486= Likely benign ★ same residue
CDH23 p.Arg2029Trp Pathogenic ★★★ ⚠ same type
CDH23 p.Asp127Gly Likely pathogenic ★★★ same type
CDH23 p.Glu956Lys Pathogenic ★★★ same type
CDH23 p.Pro240Leu Pathogenic ★★★ same type
CDH23 c.1515-12G>A Uncertain significance ★★★ same type
CDH23 p.Ala3190Val Uncertain significance ★★★ ⚠ same type

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-asp486val (accessed [today's date]).

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