ACO2 p.Ala635=
c.1905C>T · rs753933182 · VCV1590046
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
ultra-rare (popmax 0.0339%, mid)
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 -13 | GERP -3.4 |
| Overall | ||
| CADD | 1.7 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0339%
Middle Eastern · 2/5,894 alleles
Filtering AF
0.00597%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00309%
Overall
0.00204%
33/1,613,778 alleles · ultra-rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Middle Easterngrpmax | 0.0339% | 2,947 |
| African / African-American | 0.00934% | 10,704 |
| South Asian | 0.00549% | 18,214 |
| Admixed American | 0.005% | 20,003 |
| East Asian | 0.00223% | 44,900 |
| Remaining individualsnot grpmax-eligible | 0.0016% | 62,460 |
| European (non-Finnish) | 0.00119% | 84,285 |
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
- ACO2
- Protein
- p.Ala635=
- Coding
- c.1905C>T
- MANE Select
- NM_001098
- dbSNP
- rs753933182
- Type
- single nucleotide variant
- Location
- chr22:41526405 (GRCh38)
- Gene constraint
- LOEUF 0.489 · pLI 0.98 (gnomAD)
- Structure
- AlphaFold pLDDT 95.44
Similar variants
- ACO2 p.Ala635Thr Uncertain significance ★ ⚠ same residue
- ACO2 p.Arg378Ter Pathogenic/Likely pathogenic ★★ same type
- ACO2 p.Arg58Ter Pathogenic/Likely pathogenic ★★ same type
- ACO2 p.Arg84Ter Pathogenic ★★ same type
- ACO2 p.Glu464Ter Pathogenic/Likely pathogenic ★★ same type
- ACO2 p.Gly503Ter Pathogenic ★★ same type
- ACO2 c.1605+5G>C Uncertain significance ★★ same type
- ACO2 c.2208+5G>C 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/aco2-p-ala635 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown