Is EPN2 p.Thr2Arg (c.5C>G) pathogenic?

EPN2 p.Thr2Arg (c.5C>G) is classified Uncertain significance in EPN2 (ClinVar, Single submitter, 1 submitter; last evaluated 2021-08-13). AlphaMissense: likely pathogenic (0.7281); Absent from gnomAD v4.1.

How common is EPN2 p.Thr2Arg (c.5C>G) in the general population?

EPN2 p.Thr2Arg (c.5C>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about EPN2 p.Thr2Arg (c.5C>G)?

AlphaMissense predicts likely pathogenic (score 0.7281) — an in-silico prediction, not a clinical call.

EPN2 p.Thr2Arg

c.5C>G · rs764850066 · VCV2244861

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.7281 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.7281	likely pathogenic
REVEL	0.145	moderately benign-leaning
SaProt	LLR -11.63	damaging
⇒ AlphaMissense and SaProt call this damaging; REVEL does not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.7	GERP 2.4, phastCons 1
Regional constraint	o/e 0.73	unconstrained · MANE · 29 kb · p 2.8e-08 · regional, not allelic
Overall
CADD	25.0	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: EPN2
Protein: p.Thr2Arg
Coding: c.5C>G
MANE Select: NM_014964
dbSNP: rs764850066
Type: single nucleotide variant
Location: chr17:19283124 (GRCh38)
Gene constraint: LOEUF 0.804 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 60.50

Full EPN2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

EPN2 p.Ala102Thr Uncertain significance ★ ⚠ same type
EPN2 p.Ala253Gly Uncertain significance ★ ⚠ same type
EPN2 p.Ala254Asp Uncertain significance ★ same type
EPN2 p.Ala347Thr Uncertain significance ★ ⚠ same type
EPN2 p.Ala347Val Uncertain significance ★ ⚠ same type
EPN2 p.Ala412Val Uncertain significance ★ ⚠ same type
EPN2 p.Ala428Thr Uncertain significance ★ ⚠ same type
EPN2 p.Ala428Val 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/epn2-p-thr2arg (accessed [today's date]).

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