ACO1 p.His252=
c.756C>T · rs147664590 · VCV786904
Benign
Multiple submitters
Classification
Benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
rare (popmax 0.726%, afr)
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 -0.73 | GERP -4 |
| Overall | ||
| CADD | 6.527 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.726%
African / African-American · 542/74,652 alleles
Filtering AF
0.676%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.655%
Overall
0.0366%
588/1,606,552 alleles · rare
exomes 282/1,454,254 · genomes 306/152,298 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 0.726% | 138 |
| Remaining individualsnot grpmax-eligible | 0.0322% | 3,108 |
| Admixed American | 0.0254% | 3,935 |
| Middle Eastern | 0.0166% | 6,042 |
| European (non-Finnish) | 0.00085% | 117,631 |
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
- ACO1
- Protein
- p.His252=
- Coding
- c.756C>T
- MANE Select
- NM_002197
- dbSNP
- rs147664590
- Type
- single nucleotide variant
- Location
- chr9:32419135 (GRCh38)
- Gene constraint
- LOEUF 0.839 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 94.75 · 2 PDB
Similar variants
- ACO1 p.His252Tyr Uncertain significance ★ ⚠ same residue
- ACO1 p.Ala665Val Uncertain significance ★★ ⚠ same type
- ACO1 p.Arg885His Uncertain significance ★★ same type
- ACO1 p.Gly831Arg Uncertain significance ★★ ⚠ same type
- ACO1 p.Ala794= Benign ★★ same type
- ACO1 p.Asp569= Benign ★★ same type
- ACO1 p.Pro443= Benign/Likely benign ★★ same type
- ACO1 c.474+1G>T 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/aco1-p-his252 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown