ACOX3 p.Ser405=
c.1215G>A · rs140347834 · VCV731034
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.0688%, 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 -3.4 |
| Overall | ||
| CADD | 0.062 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0688%
European (non-Finnish) · 811/1,178,006 alleles
Filtering AF
0.0649%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0633%
Overall
0.054%
869/1,608,328 alleles · ultra-rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| European (non-Finnish)grpmax | 0.0688% | 1,453 |
| Middle Eastern | 0.0659% | 1,517 |
| Remaining individualsnot grpmax-eligible | 0.045% | 2,222 |
| African / African-American | 0.0134% | 7,467 |
| Admixed American | 0.012% | 8,334 |
| Ashkenazi Jewishnot grpmax-eligible | 0.00679% | 14,730 |
| Finnishnot grpmax-eligible | 0.0047% | 21,283 |
| East Asian | 0.00449% | 22,254 |
| South Asian | 0.00222% | 45,146 |
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.Ser405=
- Coding
- c.1215G>A
- MANE Select
- NM_003501
- dbSNP
- rs140347834
- Type
- single nucleotide variant
- Location
- chr4:8392418 (GRCh38)
- Gene constraint
- LOEUF 1.114 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 94.43
Similar variants
- ACOX3 p.Ser405Leu Uncertain significance ★ ⚠ same residue
- ACOX3 p.Ala28= Benign ★★ same type
- ACOX3 p.Arg75= Likely 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
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-ser405 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown