ACOX1 c.1298+252A>C
Benign
Single submitter
Classification
Benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Common
common (popmax 5.25%, 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 | ||
| Splice region | donor +252 | deep intronic (+252 nt into the intron) |
|---|---|---|
| SpliceAI | — | not assessed · no allele here is in the release |
| Constraint at this position | ||
| Conservation | phyloP 0.4 | GERP 0.18, phastCons 0.005 |
| Non-coding constraint | Z 4.28 | 1 kb window · o/e 0.70 · regional · uncalibrated |
| Overall | ||
| CADD | 6.304 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
5.25%
African / African-American · 2,179/41,532 alleles
Filtering AF
5.06%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 4.99%
Overall
1.61%
2,455/152,238 alleles · common
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 5.25% | 19 |
| Ashkenazi Jewishnot grpmax-eligible | 2.82% | 35 |
| Remaining individualsnot grpmax-eligible | 1.14% | 88 |
| Admixed American | 0.72% | 139 |
| Middle Eastern | 0.34% | 294 |
| European (non-Finnish) | 0.0618% | 1,619 |
| South Asian | 0.0207% | 4,820 |
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
- ACOX1
- Coding
- c.1298+252A>C
- MANE Select
- NM_004035
- dbSNP
- rs138269925
- Type
- single nucleotide variant
- Location
- chr17:75950522 (GRCh38)
- Gene constraint
- LOEUF 0.67 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
- Structure
- AlphaFold pLDDT 93.95
Similar variants
- ACOX1 c.538+1G>A Pathogenic/Likely pathogenic ★★ same type
- ACOX1 c.945-1G>C Likely pathogenic ★★ same type
- ACOX1 p.Arg148Ter Pathogenic ★★ same type
- ACOX1 p.Arg302Ter Pathogenic ★★ same type
- ACOX1 p.Arg94Ter Pathogenic ★★ same type
- ACOX1 p.Asn237Ser Pathogenic/Likely pathogenic ★★ same type
- ACOX1 p.Gln114Ter Pathogenic/Likely pathogenic ★★ same type
- ACOX1 p.Glu84Ter Pathogenic/Likely pathogenic ★★ 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/acox1-c-1298-plus-252a-c (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown