ACO2 c.940+13G>A
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
very rare (popmax 0.00801%, afr)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Splicing | ||
| Splice region | donor +13 | near-intronic (+13 nt from the splice site) |
|---|---|---|
| SpliceAI | — | not assessed · no allele here is in the release |
| Constraint at this position | ||
| Conservation | phyloP 2.2 | GERP 0.31, phastCons 0.97 |
| Non-coding constraint | Z 2.58 | 1 kb window · o/e 0.74 · regional · uncalibrated |
| Overall | ||
| CADD | 9.05 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00801%
African / African-American · 6/74,868 alleles
Filtering AF
0.00347%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00229%
Overall
0.000435%
7/1,610,828 alleles · very rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 0.00801% | 12,478 |
| European (non-Finnish) | 8.49e-05% | 1,177,523 |
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
- Coding
- c.940+13G>A
- MANE Select
- NM_001098
- Type
- single nucleotide variant
- Location
- chr22:41517644 (GRCh38)
- Gene constraint
- LOEUF 0.489 · pLI 0.98 (gnomAD)
- Structure
- AlphaFold pLDDT 95.44
Similar variants
- 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
- ACO2 c.2208+5G>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/aco2-c-940-plus-13g-a (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown