ACO1 p.Ile643=
c.1929C>A · VCV4683384
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
rare (popmax 0.167%, 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 0.72 | GERP -0.44, phastCons 1 |
| Overall | ||
| CADD | 6.492 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.167%
European (non-Finnish) · 1,967/1,179,204 alleles
Filtering AF
0.161%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.158%
Overall
0.129%
2,078/1,611,212 alleles · rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| European (non-Finnish)grpmax | 0.167% | 599 |
| Remaining individualsnot grpmax-eligible | 0.104% | 960 |
| Admixed American | 0.0556% | 1,800 |
| African / African-American | 0.0134% | 7,489 |
| Finnishnot grpmax-eligible | 0.00313% | 31,976 |
| South Asian | 0.00111% | 89,994 |
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.Ile643=
- Coding
- c.1929C>A
- MANE Select
- NM_002197
- Type
- single nucleotide variant
- Location
- chr9:32433805 (GRCh38)
- Gene constraint
- LOEUF 0.839 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 94.75 · 2 PDB
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-ile643 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown