Is CDH3 p.Pro47= (c.141C>G) pathogenic?

CDH3 p.Pro47= (c.141C>G) is classified Benign/Likely benign in CDH3 (ClinVar, Multiple submitters, 4 submitters; last evaluated 2026-01-13). Low-frequency (popmax 1.27%, eas); Associated with EEM syndrome.

What condition is associated with CDH3 p.Pro47= (c.141C>G)?

CDH3 p.Pro47= (c.141C>G) is associated with EEM syndrome (ClinVar).

How common is CDH3 p.Pro47= (c.141C>G) in the general population?

CDH3 p.Pro47= (c.141C>G) is low-frequency (popmax 1.27%, eas) (gnomAD).

CDH3 p.Pro47=

c.141C>G · rs74619658 · VCV731369

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

gnomAD v4.1

Rare

low-frequency (popmax 1.27%, 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 -9.6	GERP -2.5
Overall
CADD	0.236	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 1.27% East Asian · 518/40,902 alleles

Filtering AF 1.18% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.14%

Overall 0.0385% 595/1,544,556 alleles · low-frequency

Ancestry group	Frequency	1 in
East Asiangrpmax	1.27%	79
Remaining individualsnot grpmax-eligible	0.0551%	1,814
South Asian	0.0453%	2,207
Admixed American	0.00196%	50,952
European (non-Finnish)	0.000436%	229,224

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.Pro47=
Coding: c.141C>G
MANE Select: NM_001793
dbSNP: rs74619658
Type: single nucleotide variant
Location: chr16:68645731 (GRCh38)
Gene constraint: LOEUF 0.823 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 76.71 · 19 PDB

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.Pro47Thr 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
CDH3 p.Ala400Gly 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-pro47 (accessed [today's date]).

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