Is CDH3 p.Phe780= (c.2340C>T) pathogenic?

CDH3 p.Phe780= (c.2340C>T) is classified Uncertain significance in CDH3 (ClinVar, Single submitter, 1 submitter; last evaluated 2018-01-12). Very rare (popmax 0.00223%, eas); Associated with EEM syndrome.

What condition is associated with CDH3 p.Phe780= (c.2340C>T)?

CDH3 p.Phe780= (c.2340C>T) is associated with EEM syndrome (ClinVar).

How common is CDH3 p.Phe780= (c.2340C>T) in the general population?

CDH3 p.Phe780= (c.2340C>T) is very rare (popmax 0.00223%, eas) (gnomAD).

CDH3 p.Phe780=

c.2340C>T · rs1425381774 · VCV886787

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00223%, eas)

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 -4.2	GERP -4.4
Overall
CADD	8.101	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00223% East Asian · 1/44,902 alleles

Filtering AF 0.000183% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00012%

Overall 0.000558% 9/1,614,102 alleles · very rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00223%	44,902
Remaining individualsnot grpmax-eligible	0.0016%	62,482
African / African-American	0.00133%	74,942
European (non-Finnish)	0.000508%	196,674

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.Phe780=
Coding: c.2340C>T
MANE Select: NM_004933 · reported on NM_001793
dbSNP: rs1425381774
Type: single nucleotide variant
Location: chr16:68698250 (GRCh38)
Structure: AlphaFold pLDDT 78.70

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-phe780 (accessed [today's date]).

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