ACOX3 p.Arg75=
c.225C>T · rs115667291 · VCV731035
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 3 submitters
gnomAD v4.1
Rare
rare (popmax 0.313%, mid)
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 -8.2 | GERP -4.5 |
| Overall | ||
| CADD | 1.085 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.313%
Middle Eastern · 19/6,062 alleles
Filtering AF
0.206%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.203%
Overall
0.189%
3,054/1,614,192 alleles · rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Middle Easterngrpmax | 0.313% | 319 |
| Finnishnot grpmax-eligible | 0.251% | 398 |
| European (non-Finnish) | 0.213% | 470 |
| Remaining individualsnot grpmax-eligible | 0.182% | 548 |
| South Asian | 0.166% | 603 |
| Admixed American | 0.108% | 924 |
| African / African-American | 0.0453% | 2,207 |
| Ashkenazi Jewishnot grpmax-eligible | 0.00338% | 29,604 |
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
- ACOX3
- Protein
- p.Arg75=
- Coding
- c.225C>T
- MANE Select
- NM_003501
- dbSNP
- rs115667291
- Type
- single nucleotide variant
- Location
- chr4:8415919 (GRCh38)
- Gene constraint
- LOEUF 1.114 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 94.43
Similar variants
- ACOX3 p.Ala28= Benign ★★ same type
- ACOX3 p.Ala157Ser Uncertain significance ★ ⚠ same type
- ACOX3 p.Ala207Thr Uncertain significance ★ ⚠ same type
- ACOX3 p.Ala261Ser Uncertain significance ★ ⚠ same type
- ACOX3 p.Ala261Thr Uncertain significance ★ ⚠ same type
- ACOX3 p.Ala2Thr Uncertain significance ★ ⚠ same type
- ACOX3 p.Ala2Val Uncertain significance ★ ⚠ same type
- ACOX3 p.Ala361Thr 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/acox3-p-arg75 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown