Is CDH3 p.Val495Ile (c.1483G>A) pathogenic?

CDH3 p.Val495Ile (c.1483G>A) is classified Uncertain significance in CDH3 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-08-04). AlphaMissense: likely benign (0.0677); Very rare (popmax 0.000169%, nfe); Associated with Inborn genetic diseases.

What condition is associated with CDH3 p.Val495Ile (c.1483G>A)?

CDH3 p.Val495Ile (c.1483G>A) is associated with Inborn genetic diseases (ClinVar).

How common is CDH3 p.Val495Ile (c.1483G>A) in the general population?

CDH3 p.Val495Ile (c.1483G>A) is very rare (popmax 0.000169%, nfe) (gnomAD).

What do computational predictors say about CDH3 p.Val495Ile (c.1483G>A)?

AlphaMissense predicts likely benign (score 0.0677) — an in-silico prediction, not a clinical call.

CDH3 p.Val495Ile

c.1483G>A · VCV4223915

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0677 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000169%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.0677	likely benign
REVEL	0.066	moderately benign-leaning
SaProt	LLR -4.80	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.29	GERP -1.2, phastCons 0.7
Overall
CADD	3.287	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — 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

Grpmax group 0.000169% European (non-Finnish) · 2/1,180,026 alleles

Filtering AF 2.8e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.1e-05%

Overall 0.000137% 2/1,461,858 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: CDH3
Protein: p.Val495Ile
Coding: c.1483G>A
MANE Select: NM_004933 · reported on NM_001793
Type: single nucleotide variant
Location: chr16:68685263 (GRCh38)
Structure: AlphaFold pLDDT 78.70
Residue 495: the cadherin 5 domain

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.Val495Phe 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
CDH3 p.Ala64Ser Uncertain significance ★★ ⚠ same condition
CDH3 p.Ala724Ser 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-val495ile (accessed [today's date]).

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