Is EPHX1 p.Cys232Arg (c.694T>C) pathogenic?

EPHX1 p.Cys232Arg (c.694T>C) is classified Uncertain significance in EPHX1 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-08-26). AlphaMissense: likely pathogenic (0.9873); Absent from gnomAD v4.1.

How common is EPHX1 p.Cys232Arg (c.694T>C) in the general population?

EPHX1 p.Cys232Arg (c.694T>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about EPHX1 p.Cys232Arg (c.694T>C)?

AlphaMissense predicts likely pathogenic (score 0.9873) — an in-silico prediction, not a clinical call.

EPHX1 p.Cys232Arg

c.694T>C · VCV3509450

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9873 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.9873	likely pathogenic · top 1% in EPHX1
REVEL	0.197	benign-leaning
SaProt	LLR -9.62	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 4.9	GERP 1.2, phastCons 1
Regional constraint	o/e 0.96	unconstrained · MANE · 17 kb · p 0.39 · regional, not allelic
Overall
CADD	28.3	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: EPHX1
Protein: p.Cys232Arg
Coding: c.694T>C
MANE Select: NM_001136018
Type: single nucleotide variant
Location: chr1:225839318 (GRCh38)
Gene constraint: LOEUF 1.1 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 95.06

Full EPHX1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

EPHX1 c.1041-181G>A Benign ★★ same type
EPHX1 c.183+20G>A Benign ★★ same type
EPHX1 c.364+114G>C Benign ★★ same type
EPHX1 c.365-3C>A Benign ★★ same type
EPHX1 c.592+34G>A Benign ★★ same type
EPHX1 c.-5-29G>A Benign ★★ same type
EPHX1 c.-5-45G>A Benign ★★ same type
EPHX1 c.*35A>C Benign ★★ 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/ephx1-p-cys232arg (accessed [today's date]).

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