Is EPC1 p.Arg272= (c.816G>A) pathogenic?

EPC1 p.Arg272= (c.816G>A) is classified Likely benign in EPC1 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-04-12). Ultra-rare (popmax 0.051%, afr).

How common is EPC1 p.Arg272= (c.816G>A) in the general population?

EPC1 p.Arg272= (c.816G>A) is ultra-rare (popmax 0.051%, afr) (gnomAD).

EPC1 p.Arg272=

c.816G>A · VCV4018521

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.051%, afr)

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 2.9	GERP 1.7, phastCons 1
Overall
CADD	17.27	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.051% African / African-American · 38/74,572 alleles

Filtering AF 0.0382% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0337%

Overall 0.00256% 41/1,600,746 alleles · ultra-rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.051%	1,962
Admixed American	0.00341%	29,317
Remaining individualsnot grpmax-eligible	0.00161%	61,924

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: EPC1
Protein: p.Arg272=
Coding: c.816G>A
MANE Select: NM_001272004
Type: single nucleotide variant
Location: chr10:32291322 (GRCh38)
Gene constraint: LOEUF 0.229 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 57.95 · 9 PDB

Full EPC1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

EPC1 c.1863+114C>T Uncertain significance ★ ⚠ same type
EPC1 c.314-1G>T Uncertain significance ★ same type
EPC1 p.Ala229Thr Uncertain significance ★ ⚠ same type
EPC1 p.Ala604Thr Uncertain significance ★ ⚠ same type
EPC1 p.Ala770Thr Uncertain significance ★ ⚠ same type
EPC1 p.Arg238Gln Uncertain significance ★ ⚠ same type
EPC1 p.Arg336Trp Uncertain significance ★ ⚠ same type
EPC1 p.Arg405His Uncertain significance ★ ⚠ same type

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/epc1-p-arg272 (accessed [today's date]).

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