ACOX2 p.Ser418=
c.1254A>G · rs13097249 · VCV1600136
Benign
Multiple submitters
Classification
Benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Common
common (popmax 12.3%, 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 -5.8 | GERP -4.7 |
| Overall | ||
| CADD | 0.552 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
12.3%
African / African-American · 9,221/74,998 alleles
Filtering AF
12.1%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 12%
Overall
4.57%
73,735/1,614,110 alleles · common
exomes 64,005/1,461,876 · genomes 9,730/152,234 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 12.3% | 8 |
| Ashkenazi Jewishnot grpmax-eligible | 8.03% | 12 |
| Middle Eastern | 5.02% | 20 |
| Remaining individualsnot grpmax-eligible | 4.55% | 22 |
| European (non-Finnish) | 4.42% | 23 |
| Finnishnot grpmax-eligible | 4.31% | 23 |
| Admixed American | 3.45% | 29 |
| Amishnot grpmax-eligible | 3.29% | 30 |
| South Asian | 2.17% | 46 |
| East Asian | 0.0134% | 7,480 |
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.Ser418=
- Coding
- c.1254A>G
- MANE Select
- NM_003500
- dbSNP
- rs13097249
- Type
- single nucleotide variant
- Location
- chr3:58526558 (GRCh38)
- Gene constraint
- LOEUF 0.914 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 94.49
- Residue 418
- 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-ser418 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown