Is CDH23 p.Asp1259Val (c.3776A>T) pathogenic?

CDH23 p.Asp1259Val (c.3776A>T) is classified Uncertain significance in CDH23 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-01-29). AlphaMissense: ambiguous (0.3572); Very rare (popmax 0.00167%, amr); Associated with Inborn genetic diseases.

What condition is associated with CDH23 p.Asp1259Val (c.3776A>T)?

CDH23 p.Asp1259Val (c.3776A>T) is associated with Inborn genetic diseases (ClinVar).

How common is CDH23 p.Asp1259Val (c.3776A>T) in the general population?

CDH23 p.Asp1259Val (c.3776A>T) is very rare (popmax 0.00167%, amr) (gnomAD).

What do computational predictors say about CDH23 p.Asp1259Val (c.3776A>T)?

AlphaMissense predicts ambiguous (score 0.3572) — an in-silico prediction, not a clinical call.

CDH23 p.Asp1259Val

c.3776A>T · rs373300630 · VCV3141207

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.3572 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00167%, amr)

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.3572	ambiguous
REVEL	0.792	moderately pathogenic-leaning
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP 11	GERP 2.8, phastCons 1
Regional constraint	o/e 0.96	unconstrained · MANE · 359 kb · p 0.017 · regional, not allelic
Overall
CADD	25.7	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

Grpmax group 0.00167% Admixed American · 1/60,032 alleles

Overall 6.84e-05% 1/1,461,704 alleles · very rare

Rarity supports pathogenicity (ACMG PM2); frequency above a disease-specific BA1/BS1 threshold argues against it. A variant frequent in one ancestry group can be near-absent in others, so a single global figure can mislead.

Variant & gene context

Gene: CDH23
Protein: p.Asp1259Val
Coding: c.3776A>T
MANE Select: NM_001164375 · reported on NM_022124
dbSNP: rs373300630
Type: single nucleotide variant
Location: chr10:71732047 (GRCh38)

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

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

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-asp1259val (accessed [today's date]).

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