ACO2 p.Ser66fs
c.196_197del · VCV4948151
Likely pathogenic
Single submitter
Classification
Likely pathogenic
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
Consequence
frameshift
predicted LoF
gnomAD v4.1
Rare
Conditions
1
ACO2-related disorder
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Consequence | frameshift | predicted loss-of-function in a LoF-intolerant gene |
|---|---|---|
| NMD | predicted | premature termination codon in exon 3 of 18 |
| Splicing | ||
| SpliceAI | — | not assessed · substitutions only |
| Constraint at this position | ||
| Conservation | phyloP -0.52 | GERP -3, phastCons 0.03 |
Predicted loss-of-function is descriptive, not an applied PVS1 code.
Variant & gene context
- Gene
- ACO2
- Protein
- p.Ser66fs
- Coding
- c.196_197del
- MANE Select
- NM_001098
- Type
- Microsatellite
- Location
- chr22:41507810 (GRCh38)
- Gene constraint
- LOEUF 0.489 · pLI 0.98 (gnomAD)
- Structure
- AlphaFold pLDDT 95.44
Disease context
ACO2-related disorder
Similar variants
- ACO2 p.Ser239fs Pathogenic/Likely pathogenic ★★ same condition
- ACO2 p.Ser66= Likely benign ★★ same residue
- ACO2 p.Glu371fs Likely pathogenic ★ same condition
- ACO2 p.Gly240fs Likely pathogenic ★ same condition
- ACO2 p.Ser66Leu Uncertain significance ★ ⚠ same residue
- ACO2 p.Arg378Ter Pathogenic/Likely pathogenic ★★ same condition
- ACO2 p.Arg58Ter Pathogenic/Likely pathogenic ★★ same condition
- ACO2 p.Ile275fs Pathogenic/Likely pathogenic ★★ same condition
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-ser66fs (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown