Is ENOX2 p.Ile343Phe (c.1027A>T) pathogenic?

ENOX2 p.Ile343Phe (c.1027A>T) is classified Uncertain significance in ENOX2 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-09-24). AlphaMissense: likely benign (0.3228); Absent from gnomAD v4.1.

How common is ENOX2 p.Ile343Phe (c.1027A>T) in the general population?

ENOX2 p.Ile343Phe (c.1027A>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about ENOX2 p.Ile343Phe (c.1027A>T)?

AlphaMissense predicts likely benign (score 0.3228) — an in-silico prediction, not a clinical call.

ENOX2 p.Ile343Phe

c.1027A>T · VCV3508582

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.3228 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.3228	likely benign
REVEL	0.153	moderately benign-leaning
SaProt	LLR -8.81	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 6	GERP -1.3, phastCons 1
Regional constraint	o/e 0.85	unconstrained · MANE · 47 kb · p 0.0089 · regional, not allelic
Overall
CADD	20.6	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.

⚠ Isoform check: AlphaMissense numbered on a different transcript (AM I372F vs ClinVar I343F) — verify the residue.

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: ENOX2
Protein: p.Ile343Phe
Coding: c.1027A>T
MANE Select: NM_006375
Type: single nucleotide variant
Location: chrX:130656683 (GRCh38)
Structure: AlphaFold pLDDT 77.86

Full ENOX2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

ENOX2 c.1129+6G>A Benign ★★ same type
ENOX2 c.-38-6023T>G Uncertain significance ★ ⚠ same type
ENOX2 p.Arg129His Uncertain significance ★ ⚠ same type
ENOX2 p.Arg139His Uncertain significance ★ ⚠ same type
ENOX2 p.Arg156His Uncertain significance ★ ⚠ same type
ENOX2 p.Arg190His Uncertain significance ★ ⚠ same type
ENOX2 p.Arg190Leu Uncertain significance ★ ⚠ same type
ENOX2 p.Arg208His 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/enox2-p-ile343phe (accessed [today's date]).

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