Is EPHX3 p.Pro298Leu (c.893C>T) pathogenic?

EPHX3 p.Pro298Leu (c.893C>T) is classified Uncertain significance in EPHX3 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-03-13). AlphaMissense: likely benign (0.2519); Absent from gnomAD v4.1.

How common is EPHX3 p.Pro298Leu (c.893C>T) in the general population?

EPHX3 p.Pro298Leu (c.893C>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about EPHX3 p.Pro298Leu (c.893C>T)?

AlphaMissense predicts likely benign (score 0.2519) — an in-silico prediction, not a clinical call.

EPHX3 p.Pro298Leu

c.893C>T · rs2512688664 · VCV2495508

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2519 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Computational evidence

Protein change
AlphaMissense	0.2519	likely benign
REVEL	0.307	indeterminate
SaProt	LLR -11.79	damaging
⇒ SaProt calls this damaging; AlphaMissense does not; REVEL is indeterminate.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 3.1	GERP -3.1, phastCons 1
Regional constraint	o/e 0.93	unconstrained · MANE · 4,771 bp · p 0.14 · regional, not allelic
Overall
CADD	23.5	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: EPHX3
Protein: p.Pro298Leu
Coding: c.893C>T
MANE Select: NM_024794
dbSNP: rs2512688664
Type: single nucleotide variant
Location: chr19:15227627 (GRCh38)
Gene constraint: LOEUF 1.166 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 94.38

Full EPHX3 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

EPHX3 p.Ala176Asp Uncertain significance ★ ⚠ same type
EPHX3 p.Ala176Thr Uncertain significance ★ ⚠ same type
EPHX3 p.Ala22Ser Uncertain significance ★ ⚠ same type
EPHX3 p.Ala65Ser Uncertain significance ★ ⚠ same type
EPHX3 p.Ala65Thr Uncertain significance ★ ⚠ same type
EPHX3 p.Arg114Cys Uncertain significance ★ ⚠ same type
EPHX3 p.Arg114His Uncertain significance ★ ⚠ same type
EPHX3 p.Arg118Gln 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/ephx3-p-pro298leu (accessed [today's date]).

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