Is ALOX12 p.Pro337Arg (c.1010C>G) pathogenic?

ALOX12 p.Pro337Arg (c.1010C>G) is classified Uncertain significance in ALOX12 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-08-08). AlphaMissense: likely benign (0.1086); Ultra-rare (popmax 0.029%, eas).

How common is ALOX12 p.Pro337Arg (c.1010C>G) in the general population?

ALOX12 p.Pro337Arg (c.1010C>G) is ultra-rare (popmax 0.029%, eas) (gnomAD).

What do computational predictors say about ALOX12 p.Pro337Arg (c.1010C>G)?

AlphaMissense predicts likely benign (score 0.1086) — an in-silico prediction, not a clinical call.

ALOX12 p.Pro337Arg

c.1010C>G · rs183466632 · VCV2394557

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1086 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.029%, eas)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1086	likely benign
REVEL	0.216	benign-leaning
SaProt	LLR -10.17	damaging
⇒ SaProt calls this damaging; AlphaMissense and REVEL do not.
Splicing
SpliceAI	Δ0.21	acceptor gain · deltas
Constraint at this position
Conservation	phyloP 4	GERP 1.3, phastCons 0.99
Regional constraint	o/e 0.88	unconstrained · MANE · 14 kb · p 0.00031 · regional, not allelic
Overall
CADD	24.0	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

Grpmax group 0.029% East Asian · 13/44,904 alleles

Filtering AF 0.0171% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0136%

Overall 0.00204% 33/1,614,080 alleles · ultra-rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.029%	3,454
African / African-American	0.00534%	18,728
Remaining individualsnot grpmax-eligible	0.0032%	31,243
Admixed American	0.00167%	60,008
European (non-Finnish)	0.0011%	90,772

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: ALOX12
Protein: p.Pro337Arg
Coding: c.1010C>G
MANE Select: NM_000697
dbSNP: rs183466632
Type: single nucleotide variant
Location: chr17:7001660 (GRCh38)
Gene constraint: LOEUF 0.921 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 95.45 · 5 PDB
Residue 337: the lipoxygenase domain; an α-helix

Full ALOX12 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

ALOX12 c.1161+228C>T Benign ★★ same type
ALOX12 c.135+58C>T Benign ★★ same type
ALOX12 c.136-69G>A Benign ★★ same type
ALOX12 c.1418+32C>T Benign ★★ same type
ALOX12 c.1541-20G>A Benign ★★ same type
ALOX12 c.1541-264T>A Benign ★★ same type
ALOX12 c.337+16C>T Benign ★★ same type
ALOX12 c.337+37T>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/alox12-p-pro337arg (accessed [today's date]).

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