ACO2 p.Arg424=
c.1272C>T · rs368067033 · VCV1099929
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
ultra-rare (popmax 0.0134%, eas)
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 -14 | GERP -3.7 |
| Overall | ||
| CADD | 0.835 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0134%
East Asian · 6/44,902 alleles
Filtering AF
0.00578%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00394%
Overall
0.00173%
28/1,614,088 alleles · ultra-rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| East Asiangrpmax | 0.0134% | 7,484 |
| Remaining individualsnot grpmax-eligible | 0.0112% | 8,926 |
| Admixed American | 0.01% | 10,002 |
| South Asian | 0.00439% | 22,773 |
| African / African-American | 0.00133% | 74,940 |
| European (non-Finnish) | 0.000339% | 295,012 |
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.Arg424=
- Coding
- c.1272C>T
- MANE Select
- NM_001098
- dbSNP
- rs368067033
- Type
- single nucleotide variant
- Location
- chr22:41522963 (GRCh38)
- Gene constraint
- LOEUF 0.489 · pLI 0.98 (gnomAD)
- Structure
- AlphaFold pLDDT 95.44
Similar variants
- ACO2 p.Arg424His Uncertain significance ★★ ⚠ same residue
- ACO2 p.Arg424Cys Uncertain significance ★ ⚠ same residue
- ACO2 p.Arg424Ser 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
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-arg424 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown