ACO2 p.Ile742=
c.2226C>T · rs771726944 · VCV385150
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 3 submitters
gnomAD v4.1
Rare
ultra-rare (popmax 0.0292%, 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 4 | GERP 0.73, phastCons 1 |
| Overall | ||
| CADD | 11.66 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0292%
European (non-Finnish) · 344/1,180,022 alleles
Filtering AF
0.0265%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0255%
Overall
0.0216%
349/1,612,238 alleles · ultra-rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| European (non-Finnish)grpmax | 0.0292% | 3,430 |
| Remaining individualsnot grpmax-eligible | 0.00481% | 20,777 |
| African / African-American | 0.00134% | 74,866 |
| South Asian | 0.0011% | 91,008 |
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.Ile742=
- Coding
- c.2226C>T
- MANE Select
- NM_001098
- dbSNP
- rs771726944
- Type
- single nucleotide variant
- Location
- chr22:41528496 (GRCh38)
- Gene constraint
- LOEUF 0.489 · pLI 0.98 (gnomAD)
- Structure
- AlphaFold pLDDT 95.44
Similar variants
- ACO2 p.Ile742del 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-ile742 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown