ACO2 p.Ser239=
c.717C>T · rs138803847 · VCV2874542
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
very rare (popmax 0.00445%, eas)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Splicing | ||
| SpliceAI | <0.2 | all four deltas below 0.2 · C>A here scores Δ0.45 · evaluated, not missing |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP -13 | GERP -3.4 |
| Overall | ||
| CADD | 3.386 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00445%
East Asian · 2/44,898 alleles
Filtering AF
0.000763%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.000605%
Overall
0.0013%
21/1,613,938 alleles · very rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| East Asiangrpmax | 0.00445% | 22,449 |
| African / African-American | 0.00267% | 37,457 |
| Remaining individualsnot grpmax-eligible | 0.0016% | 62,480 |
| European (non-Finnish) | 0.00127% | 78,670 |
| South Asian | 0.0011% | 91,082 |
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.Ser239=
- Coding
- c.717C>T
- MANE Select
- NM_001098
- dbSNP
- rs138803847
- Type
- single nucleotide variant
- Location
- chr22:41515799 (GRCh38)
- Gene constraint
- LOEUF 0.489 · pLI 0.98 (gnomAD)
- Structure
- AlphaFold pLDDT 95.44
Similar variants
- ACO2 p.Ser239fs Pathogenic/Likely pathogenic ★★ 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-ser239 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown