ACOX2 p.Asp594=
c.1782C>T · rs142302007 · VCV2414037
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
ultra-rare (popmax 0.0164%, 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 -3 | GERP -4 |
| Overall | ||
| CADD | 3.895 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0164%
European (non-Finnish) · 193/1,180,042 alleles
Filtering AF
0.0144%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0137%
Overall
0.0134%
217/1,614,078 alleles · ultra-rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| European (non-Finnish)grpmax | 0.0164% | 6,114 |
| Admixed American | 0.015% | 6,666 |
| African / African-American | 0.00801% | 12,489 |
| Remaining individualsnot grpmax-eligible | 0.008% | 12,497 |
| South Asian | 0.00439% | 22,772 |
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
- ACOX2
- Protein
- p.Asp594=
- Coding
- c.1782C>T
- MANE Select
- NM_003500
- dbSNP
- rs142302007
- Type
- single nucleotide variant
- Location
- chr3:58517274 (GRCh38)
- Gene constraint
- LOEUF 0.914 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 94.49
- Residue 594
- a UniProt-annotated variant site (in cbas6; patient liver samples show absence of the protein; complete loss of fatty acid beta-oxidation activity)
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-asp594 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown