Is EPC1 p.Ile301Val (c.901A>G) pathogenic?

EPC1 p.Ile301Val (c.901A>G) is classified Uncertain significance in EPC1 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-08-09). AlphaMissense: likely benign (0.0551); Ultra-rare (popmax 0.0183%, amr).

How common is EPC1 p.Ile301Val (c.901A>G) in the general population?

EPC1 p.Ile301Val (c.901A>G) is ultra-rare (popmax 0.0183%, amr) (gnomAD).

What do computational predictors say about EPC1 p.Ile301Val (c.901A>G)?

AlphaMissense predicts likely benign (score 0.0551) — an in-silico prediction, not a clinical call.

EPC1 p.Ile301Val

c.901A>G · rs748526235 · VCV2596157

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0551 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0183%, amr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0551	likely benign
REVEL	0.03	moderately benign-leaning
SaProt	LLR -5.64	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 2.1	GERP 2.1, phastCons 1
Regional constraint	o/e 0.89	unconstrained · MANE · 19 kb · p 0.02 · regional, not allelic
Overall
CADD	15.76	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0183% Admixed American · 11/59,998 alleles

Filtering AF 0.0102% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00785%

Overall 0.00446% 72/1,613,954 alleles · ultra-rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.0183%	5,454
Middle Eastern	0.0164%	6,080
South Asian	0.0143%	7,007
Remaining individualsnot grpmax-eligible	0.0096%	10,413
European (non-Finnish)	0.00347%	28,779

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.Ile301Val
Coding: c.901A>G
MANE Select: NM_001272004
dbSNP: rs748526235
Type: single nucleotide variant
Location: chr10:32291237 (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-ile301val (accessed [today's date]).

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