Is ACOX2 p.Ser588= (c.1764G>A) pathogenic?

ACOX2 p.Ser588= (c.1764G>A) is classified Likely benign in ACOX2 (ClinVar, Single submitter, 3 submitters; last evaluated 2025-10-27). Ultra-rare (popmax 0.0399%, nfe).

How common is ACOX2 p.Ser588= (c.1764G>A) in the general population?

ACOX2 p.Ser588= (c.1764G>A) is ultra-rare (popmax 0.0399%, nfe) (gnomAD).

ACOX2 p.Ser588=

c.1764G>A · rs144682871 · VCV1571094

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 3 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0399%, nfe)

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 -20	GERP -4
Overall
CADD	0.438	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0399% European (non-Finnish) · 471/1,180,036 alleles

Filtering AF 0.0369% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0357%

Overall 0.0318% 514/1,614,164 alleles · ultra-rare

Ancestry group	Frequency	1 in
Ashkenazi Jewishnot grpmax-eligible	0.0439%	2,278
European (non-Finnish)grpmax	0.0399%	2,505
Remaining individualsnot grpmax-eligible	0.0192%	5,209
Middle Eastern	0.0165%	6,060
African / African-American	0.0133%	7,503
Admixed American	0.00833%	12,002
Finnishnot grpmax-eligible	0.00156%	64,036
South Asian	0.0011%	91,080

Ashkenazi Jewish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Ser588=
Coding: c.1764G>A
MANE Select: NM_003500
dbSNP: rs144682871
Type: single nucleotide variant
Location: chr3:58517292 (GRCh38)
Gene constraint: LOEUF 0.914 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 94.49
Residue 588: 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.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
ACOX2 p.Arg323His 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-ser588 (accessed [today's date]).

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