ACOX2 p.Leu443=
c.1329C>T · rs112570370 · VCV2912420
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
ultra-rare (popmax 0.0333%, afr)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation/SpliceAI carries the signal. | ||
| Splicing | ||
| SpliceAI | Δ0.26 | donor gain · deltas |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP 0.34 | GERP -4.1, phastCons 0.98 |
| Overall | ||
| CADD | 12.35 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0333%
African / African-American · 25/75,052 alleles
Filtering AF
0.0231%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0197%
Overall
0.00248%
40/1,613,632 alleles · ultra-rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 0.0333% | 3,002 |
| Remaining individualsnot grpmax-eligible | 0.0176% | 5,681 |
| South Asian | 0.0022% | 45,476 |
| European (non-Finnish) | 0.00017% | 589,870 |
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.Leu443=
- Coding
- c.1329C>T
- MANE Select
- NM_003500
- dbSNP
- rs112570370
- Type
- single nucleotide variant
- Location
- chr3:58526483 (GRCh38)
- Gene constraint
- LOEUF 0.914 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 94.49
- Residue 443
- 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.Leu443Phe 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-leu443 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown