Is EPCAM p.Pro3= (c.9C>T) pathogenic?

EPCAM p.Pro3= (c.9C>T) is classified Likely benign in EPCAM (ClinVar, Single submitter, 1 submitter; last evaluated 2022-08-09). Ultra-rare (popmax 0.0427%, sas); Associated with hereditary neoplastic syndrome.

What condition is associated with EPCAM p.Pro3= (c.9C>T)?

EPCAM p.Pro3= (c.9C>T) is associated with hereditary neoplastic syndrome (ClinVar).

How common is EPCAM p.Pro3= (c.9C>T) in the general population?

EPCAM p.Pro3= (c.9C>T) is ultra-rare (popmax 0.0427%, sas) (gnomAD).

EPCAM p.Pro3=

c.9C>T · rs532872105 · VCV1768925

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.0427%, sas)

Conditions

hereditary neoplastic 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 -0.39	GERP -2
Overall
CADD	10.85	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0427% South Asian · 36/84,352 alleles

Filtering AF 0.0317% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0278%

Overall 0.0025% 39/1,559,482 alleles · ultra-rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0427%	2,343
Remaining individualsnot grpmax-eligible	0.0033%	30,279
European (non-Finnish)	8.63e-05%	1,158,949

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: EPCAM
Protein: p.Pro3=
Coding: c.9C>T
MANE Select: NM_002354
dbSNP: rs532872105
Type: single nucleotide variant
Location: chr2:47369514 (GRCh38)
Gene constraint: LOEUF 1.341 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 87.71 · 2 PDB

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

Disease context

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

Similar variants

EPCAM p.Pro3Leu Uncertain significance ★ ⚠ same residue
EPCAM p.Pro3Thr Uncertain significance ★ ⚠ same residue
EPCAM p.Pro3Ser Uncertain significance ★ ⚠ same residue
EPCAM c.491+1G>A Pathogenic ★★ same condition
EPCAM p.Ala22Thr Uncertain significance ★★ ⚠ same condition
EPCAM p.Ala256Ser Uncertain significance ★★ ⚠ same condition
EPCAM p.Ala278Val Uncertain significance ★★ same condition
EPCAM p.Ala87Val 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/epcam-p-pro3 (accessed [today's date]).

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