ACO1 p.Asp868=
c.2604T>C · VCV4683385
Benign
Single submitter
Classification
Benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Common
common (popmax 13.1%, 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 | ||
| SpliceAI | — | not assessed · no allele here is in the release |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP -6.4 | GERP -3.9 |
| Overall | ||
| CADD | 0.413 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
13.1%
African / African-American · 9,853/74,998 alleles
Filtering AF
12.9%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 12.8%
Overall
0.855%
13,795/1,614,072 alleles · common
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 13.1% | 8 |
| Middle Eastern | 2.5% | 40 |
| Admixed American | 1.45% | 69 |
| Remaining individualsnot grpmax-eligible | 1.37% | 73 |
| Ashkenazi Jewishnot grpmax-eligible | 0.936% | 107 |
| Amishnot grpmax-eligible | 0.329% | 304 |
| European (non-Finnish) | 0.145% | 690 |
| South Asian | 0.078% | 1,283 |
| Finnishnot grpmax-eligible | 0.00156% | 64,040 |
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.Asp868=
- Coding
- c.2604T>C
- MANE Select
- NM_002197
- Type
- single nucleotide variant
- Location
- chr9:32450045 (GRCh38)
- Gene constraint
- LOEUF 0.839 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 94.75 · 2 PDB
- Residue 868
- 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 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-asp868 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown