Is EPC2 p.Val694Leu (c.2080G>T) pathogenic?

EPC2 p.Val694Leu (c.2080G>T) is classified Uncertain significance in EPC2 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-02-28). AlphaMissense: likely benign (0.2064); Absent from gnomAD v4.1.

How common is EPC2 p.Val694Leu (c.2080G>T) in the general population?

EPC2 p.Val694Leu (c.2080G>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about EPC2 p.Val694Leu (c.2080G>T)?

AlphaMissense predicts likely benign (score 0.2064) — an in-silico prediction, not a clinical call.

EPC2 p.Val694Leu

c.2080G>T · rs1485366788 · VCV3089467

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2064 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.2064	likely benign
REVEL	0.208	benign-leaning
SaProt	LLR -7.06	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 12	GERP 2.8, phastCons 1
Regional constraint	o/e 0.79	unconstrained · MANE · 4,667 bp · p 0.00092 · regional, not allelic
Overall
CADD	22.5	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

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.Val694Leu
Coding: c.2080G>T
MANE Select: NM_015630
dbSNP: rs1485366788
Type: single nucleotide variant
Location: chr2:148784730 (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.Ala14Asp Uncertain significance ★ ⚠ same type
EPC2 p.Ala634Thr Uncertain significance ★ ⚠ same type
EPC2 p.Ala711Thr 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-val694leu (accessed [today's date]).

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