Is EPCAM p.Ser260= (c.780A>T) pathogenic?

EPCAM p.Ser260= (c.780A>T) is classified Likely benign in EPCAM (ClinVar, Single submitter, 1 submitter; last evaluated 2026-04-22). Absent from gnomAD v4.1; Associated with hereditary neoplastic syndrome.

What condition is associated with EPCAM p.Ser260= (c.780A>T)?

EPCAM p.Ser260= (c.780A>T) is associated with hereditary neoplastic syndrome (ClinVar).

How common is EPCAM p.Ser260= (c.780A>T) in the general population?

EPCAM p.Ser260= (c.780A>T) is absent from gnomAD v4.1 (gnomAD).

EPCAM p.Ser260=

c.780A>T · VCV4870521

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Absent

absent from gnomAD v4.1

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 0.001	GERP -5.9, phastCons 0.033
Overall
CADD	5.741	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: EPCAM
Protein: p.Ser260=
Coding: c.780A>T
MANE Select: NM_002354
Type: single nucleotide variant
Location: chr2:47379891 (GRCh38)
Gene constraint: LOEUF 1.341 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 87.71 · 2 PDB
Residue 260: a UniProt-annotated variant site (in diar5; likely pathogenic)

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.Ser260Leu 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
EPCAM p.Arg173Cys Uncertain significance ★★ ⚠ same condition
EPCAM p.Arg293Lys 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-ser260 (accessed [today's date]).

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