Is ALOX15 p.Pro384Arg (c.1151C>G) pathogenic?

ALOX15 p.Pro384Arg (c.1151C>G) is classified Uncertain significance in ALOX15 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-03-03). AlphaMissense: likely pathogenic (0.7767); Very rare (popmax 8.47e-05%, nfe).

How common is ALOX15 p.Pro384Arg (c.1151C>G) in the general population?

ALOX15 p.Pro384Arg (c.1151C>G) is very rare (popmax 8.47e-05%, nfe) (gnomAD).

What do computational predictors say about ALOX15 p.Pro384Arg (c.1151C>G)?

AlphaMissense predicts likely pathogenic (score 0.7767) — an in-silico prediction, not a clinical call.

ALOX15 p.Pro384Arg

c.1151C>G · VCV3858052

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.7767 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 8.47e-05%, nfe)

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.7767	likely pathogenic · top 10% in ALOX15
REVEL	0.626	indeterminate
SaProt	LLR -13.97	damaging
⇒ AlphaMissense and SaProt both call this damaging; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.5	GERP 1.7, phastCons 1
Regional constraint	o/e 0.96	unconstrained · MANE · 5,655 bp · p 0.39 · regional, not allelic
Overall
CADD	25.4	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — 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

Grpmax group 8.47e-05% European (non-Finnish) · 1/1,180,030 alleles

Overall 6.84e-05% 1/1,461,852 alleles · very rare

Rarity supports pathogenicity (ACMG PM2); frequency above a disease-specific BA1/BS1 threshold argues against it. A variant frequent in one ancestry group can be near-absent in others, so a single global figure can mislead.

Variant & gene context

Gene: ALOX15
Protein: p.Pro384Arg
Coding: c.1151C>G
MANE Select: NM_001140
Type: single nucleotide variant
Location: chr17:4635769 (GRCh38)
Gene constraint: LOEUF 1.117 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 95.46
Residue 384: the lipoxygenase domain

Full ALOX15 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

ALOX15 p.Pro384Leu Uncertain significance ★ ⚠ same residue
ALOX15 p.Gly102Val Uncertain significance ★★ ⚠ same type
ALOX15 c.1418+9A>G Benign ★★ same type
ALOX15 p.Arg205Gln Benign ★★ ⚠ same type
ALOX15 p.Arg348= Benign ★★ same type
ALOX15 p.Asn103Lys Benign ★★ same type
ALOX15 p.Asp90His Likely benign ★★ same type
ALOX15 p.Pro565= 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/alox15-p-pro384arg (accessed [today's date]).

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