ACO1 p.Pro443=
c.1329G>A · rs112535632 · VCV732276
Benign/Likely benign
Multiple submitters
Classification
Benign/Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 3 submitters
gnomAD v4.1
Rare
rare (popmax 0.501%, 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 -7.5 | GERP -4.8 |
| Overall | ||
| CADD | 0.659 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.501%
African / African-American · 376/75,014 alleles
Filtering AF
0.459%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.443%
Overall
0.0402%
648/1,613,686 alleles · rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 0.501% | 200 |
| Middle Eastern | 0.215% | 466 |
| Ashkenazi Jewishnot grpmax-eligible | 0.111% | 897 |
| Remaining individualsnot grpmax-eligible | 0.0832% | 1,202 |
| Admixed American | 0.0433% | 2,307 |
| East Asian | 0.0178% | 5,608 |
| European (non-Finnish) | 0.0113% | 8,871 |
| South Asian | 0.00659% | 15,171 |
| Finnishnot grpmax-eligible | 0.00156% | 63,962 |
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.Pro443=
- Coding
- c.1329G>A
- MANE Select
- NM_002197
- dbSNP
- rs112535632
- Type
- single nucleotide variant
- Location
- chr9:32425978 (GRCh38)
- Gene constraint
- LOEUF 0.839 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 94.75 · 2 PDB
- Residue 443
- an α-helix
Similar variants
- 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.His252= Benign ★★ same type
- ACO1 c.474+1G>T Uncertain significance ★ same type
- ACO1 p.Ala286Val 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-pro443 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown