Is ACOX2 p.Ala388= (c.1164A>G) pathogenic?

ACOX2 p.Ala388= (c.1164A>G) is classified Benign in ACOX2 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2026-02-03). Common (popmax 29.3%, afr) — too common for a highly-penetrant pathogenic allele.

ACOX2 p.Ala388=

Q: How common is ACOX2 p.Ala388= (c.1164A>G) in the general population?

ACOX2 p.Ala388= (c.1164A>G) is common (popmax 29.3%, afr) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.1164A>G · rs1127743 · VCV1571341

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Common

common (popmax 29.3%, afr) — too common for a highly-penetrant pathogenic allele

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -7.3	GERP -4.7
Overall
CADD	0.263	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 29.3% African / African-American · 21,922/74,936 alleles

Filtering AF 28.9% ClinGen BA1/BS1 input FAF95, joint · FAF99 28.8%

Overall 6.74% 108,790/1,613,488 alleles · common

Ancestry group	Frequency	1 in
African / African-Americangrpmax	29.3%	3
East Asian	21.4%	5
Middle Eastern	15.7%	6
South Asian	8.84%	11
Admixed American	8.47%	12
Remaining individualsnot grpmax-eligible	8.38%	12
Ashkenazi Jewishnot grpmax-eligible	7.75%	13
Amishnot grpmax-eligible	6.48%	15
European (non-Finnish)	4.56%	22
Finnishnot grpmax-eligible	2.85%	35

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: ACOX2
Protein: p.Ala388=
Coding: c.1164A>G
MANE Select: NM_003500
dbSNP: rs1127743
Type: single nucleotide variant
Location: chr3:58526648 (GRCh38)
Gene constraint: LOEUF 0.914 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 94.49
Residue 388: a UniProt-annotated variant site (in cbas6; patient liver samples show absence of the protein; complete loss of fatty acid beta-oxidation activity)

Full ACOX2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

ACOX2 p.Ala388Thr Uncertain significance ★ ⚠ same residue
ACOX2 p.Ala106Val Uncertain significance ★★ ⚠ same type
ACOX2 p.Ala48Glu Uncertain significance ★★ ⚠ same type
ACOX2 p.Arg197Gln Uncertain significance ★★ ⚠ same type
ACOX2 p.Arg197Trp Uncertain significance ★★ ⚠ same type
ACOX2 p.Arg215Trp Uncertain significance ★★ ⚠ same type
ACOX2 p.Arg318His Uncertain significance ★★ ⚠ same type
ACOX2 p.Arg323Cys 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/acox2-p-ala388 (accessed [today's date]).

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