Is EPC2 p.Ala14Asp (c.41C>A) pathogenic?

EPC2 p.Ala14Asp (c.41C>A) is classified Uncertain significance in EPC2 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-07-14). AlphaMissense: likely pathogenic (0.9813); Absent from gnomAD v4.1.

How common is EPC2 p.Ala14Asp (c.41C>A) in the general population?

EPC2 p.Ala14Asp (c.41C>A) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about EPC2 p.Ala14Asp (c.41C>A)?

AlphaMissense predicts likely pathogenic (score 0.9813) — an in-silico prediction, not a clinical call.

EPC2 p.Ala14Asp

c.41C>A · VCV4249659

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9813 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.9813	likely pathogenic
REVEL	0.214	benign-leaning
SaProt	LLR -8.65	tolerated
⇒ AlphaMissense calls this damaging; REVEL and SaProt do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.4	GERP 5.2, phastCons 1
Regional constraint	o/e 0.43	unconstrained · MANE · 45 kb · p 1.6e-07 · regional, not allelic
Overall
CADD	27.1	PHRED · no single calibrated threshold — expert panels disagree

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

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: EPC2
Protein: p.Ala14Asp
Coding: c.41C>A
MANE Select: NM_015630
Type: single nucleotide variant
Location: chr2:148645058 (GRCh38)
Gene constraint: LOEUF 0.203 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 58.35

Full EPC2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

EPC2 c.666+9C>T Benign ★★ same type
EPC2 p.Arg253= Benign ★★ same type
EPC2 p.Phe6= Benign ★★ same type
EPC2 p.Ser611= Benign ★★ same type
EPC2 p.Ala13Thr Uncertain significance ★ ⚠ same type
EPC2 p.Ala634Thr Uncertain significance ★ ⚠ same type
EPC2 p.Ala711Thr Uncertain significance ★ ⚠ same type
EPC2 p.Ala711Val 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/epc2-p-ala14asp (accessed [today's date]).

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