Is CDH3 p.Asp775Val (c.2324A>T) pathogenic?

CDH3 p.Asp775Val (c.2324A>T) is classified Uncertain significance in CDH3 (ClinVar, Single submitter, 1 submitter; last evaluated 2021-06-18). AlphaMissense: likely pathogenic (0.9479); Absent from gnomAD v4.1; Associated with Inborn genetic diseases.

What condition is associated with CDH3 p.Asp775Val (c.2324A>T)?

CDH3 p.Asp775Val (c.2324A>T) is associated with Inborn genetic diseases (ClinVar).

How common is CDH3 p.Asp775Val (c.2324A>T) in the general population?

CDH3 p.Asp775Val (c.2324A>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about CDH3 p.Asp775Val (c.2324A>T)?

AlphaMissense predicts likely pathogenic (score 0.9479) — an in-silico prediction, not a clinical call.

CDH3 p.Asp775Val

c.2324A>T · rs2543772451 · VCV2233199

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9479 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.9479	likely pathogenic · top 7% in CDH3
REVEL	0.941	strongly pathogenic-leaning
SaProt	LLR -14.80	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 11	GERP 2.2, phastCons 1
Overall
CADD	27.5	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: CDH3
Protein: p.Asp775Val
Coding: c.2324A>T
MANE Select: NM_004933 · reported on NM_001793
dbSNP: rs2543772451
Type: single nucleotide variant
Location: chr16:68698234 (GRCh38)
Structure: AlphaFold pLDDT 78.70

Full CDH3 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

Similar variants

CDH3 p.Asp775Asn Uncertain significance ★★ ⚠ same residue
CDH15 p.Arg775Gln Likely benign ★★ same residue
CDH3 p.Asp775Tyr Uncertain significance ★ ⚠ same residue
CDH3 p.Ala150Thr Uncertain significance ★★ ⚠ same condition
CDH3 p.Ala22Glu Uncertain significance ★★ ⚠ same condition
CDH3 p.Ala356Pro Uncertain significance ★★ ⚠ same condition
CDH3 p.Ala361Ser Uncertain significance ★★ ⚠ same condition
CDH3 p.Ala361Val 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/cdh3-p-asp775val (accessed [today's date]).

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