ACO1 p.Pro92=
c.276C>T · VCV4683378
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
rare (popmax 0.602%, sas)
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 -0.41 | GERP -4.8, phastCons 0.001 |
| Overall | ||
| CADD | 9.942 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.602%
South Asian · 548/91,074 alleles
Filtering AF
0.56%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.544%
Overall
0.04%
645/1,614,006 alleles · rare
exomes 603/1,461,778 · genomes 42/152,228 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| South Asiangrpmax | 0.602% | 166 |
| Remaining individualsnot grpmax-eligible | 0.0656% | 1,525 |
| Ashkenazi Jewishnot grpmax-eligible | 0.0608% | 1,644 |
| Middle Eastern | 0.033% | 3,030 |
| African / African-American | 0.0253% | 3,948 |
| Admixed American | 0.00667% | 15,002 |
| East Asian | 0.00223% | 44,860 |
| European (non-Finnish) | 0.00102% | 98,330 |
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.Pro92=
- Coding
- c.276C>T
- MANE Select
- NM_002197
- Type
- single nucleotide variant
- Location
- chr9:32408523 (GRCh38)
- Gene constraint
- LOEUF 0.839 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 94.75 · 2 PDB
- Residue 92
- 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-pro92 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown