Is CDH3 p.Leu687= (c.2061C>T) pathogenic?

CDH3 p.Leu687= (c.2061C>T) is classified Conflicting classifications of pathogenicity in CDH3 (ClinVar, Conflicting submitters, 2 submitters; last evaluated 2022-11-28). Ultra-rare (popmax 0.01%, amr); Associated with EEM syndrome.

What condition is associated with CDH3 p.Leu687= (c.2061C>T)?

CDH3 p.Leu687= (c.2061C>T) is associated with EEM syndrome (ClinVar).

How common is CDH3 p.Leu687= (c.2061C>T) in the general population?

CDH3 p.Leu687= (c.2061C>T) is ultra-rare (popmax 0.01%, amr) (gnomAD).

CDH3 p.Leu687=

c.2061C>T · rs1567457224 · VCV885773

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.01%, amr)

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 -0.97	GERP -4.4, phastCons 0.007
Overall
CADD	2.313	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.01% Admixed American · 6/59,966 alleles

Filtering AF 0.00429% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00295%

Overall 0.000372% 6/1,613,956 alleles · ultra-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.Leu687=
Coding: c.2061C>T
MANE Select: NM_004933 · reported on NM_001793
dbSNP: rs1567457224
Type: single nucleotide variant
Location: chr16:68695313 (GRCh38)
Structure: AlphaFold pLDDT 78.70
Residue 687: the 'disordered' region

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.Leu687Ile Uncertain significance ★ same residue
CDH3 p.Leu687Val Uncertain significance ★ ⚠ same residue
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

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-leu687 (accessed [today's date]).

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