Is CDH3 p.Val428= (c.1284G>A) pathogenic?

CDH3 p.Val428= (c.1284G>A) is classified Uncertain significance in CDH3 (ClinVar, Single submitter, 1 submitter; last evaluated 2017-04-27). Very rare (popmax 0.00169%, nfe); Associated with EEM syndrome.

What condition is associated with CDH3 p.Val428= (c.1284G>A)?

CDH3 p.Val428= (c.1284G>A) is associated with EEM syndrome (ClinVar).

How common is CDH3 p.Val428= (c.1284G>A) in the general population?

CDH3 p.Val428= (c.1284G>A) is very rare (popmax 0.00169%, nfe) (gnomAD).

CDH3 p.Val428=

c.1284G>A · rs911987634 · VCV886725

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00169%, nfe)

Conditions

EEM syndrome

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 2.5	GERP -0.2, phastCons 1
Overall
CADD	7.767	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00169% European (non-Finnish) · 20/1,180,052 alleles

Filtering AF 0.00111% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0009%

Overall 0.00124% 20/1,614,078 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.Val428=
Coding: c.1284G>A
MANE Select: NM_001793
dbSNP: rs911987634
Type: single nucleotide variant
Location: chr16:68684684 (GRCh38)
Gene constraint: LOEUF 0.823 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 76.71 · 19 PDB
Residue 428: the cadherin 3 domain

Full CDH3 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

EEM syndrome — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

CDH3 p.Glu708Ter Likely pathogenic ★★ same condition
CDH3 c.1571-7C>G Uncertain significance ★★ same condition
CDH3 c.45+6C>T Uncertain significance ★★ same condition
CDH3 c.867+6T>C Uncertain significance ★★ same condition
CDH3 p.Ala159Thr Uncertain significance ★★ ⚠ same condition
CDH3 p.Ala34Thr Uncertain significance ★★ ⚠ same condition
CDH3 p.Ala400Gly Uncertain significance ★★ ⚠ same condition
CDH3 p.Ala414Thr 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-val428 (accessed [today's date]).

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