MCCC2 p.Ala430=
c.1290C>A · rs1407751176 · VCV1083036
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Absent
absent from gnomAD v4.1
Conditions
1
3-methylcrotonyl-CoA carboxylase 2 deficiency
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 0.77 | GERP -0.095, phastCons 1 |
| Overall | ||
| CADD | 8.08 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.
Variant & gene context
- Gene
- MCCC2
- Protein
- p.Ala430=
- Coding
- c.1290C>A
- MANE Select
- NM_022132
- dbSNP
- rs1407751176
- Type
- single nucleotide variant
- Location
- chr5:71649170 (GRCh38)
- Gene constraint
- LOEUF 0.832 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 94.82 · 14 PDB
- Residue 430
- an α-helix; the coa carboxyltransferase c-terminal domain; the 'carboxyltransferase' region
Disease context
3-methylcrotonyl-CoA carboxylase 2 deficiency — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatmentsFor 3-methylcrotonyl-CoA carboxylase deficiency (Orphanet):
- Inheritance
- Autosomal recessive
- Onset
- All ages
- Prevalence
- 1-9 / 100 000 (Europe)
Similar variants
- MCCC2 c.1000-2A>G Likely pathogenic ★★ same condition
- MCCC2 c.1072+1G>A Likely pathogenic ★★ same condition
- MCCC2 c.1149+1G>A Pathogenic/Likely pathogenic ★★ same condition
- MCCC2 c.1149+1G>T Pathogenic/Likely pathogenic ★★ same condition
- MCCC2 c.1216+1G>A Likely pathogenic ★★ same condition
- MCCC2 c.1216+2T>A Pathogenic/Likely pathogenic ★★ same condition
- MCCC2 c.1216+2T>C Likely pathogenic ★★ same condition
- MCCC2 c.129+1G>T 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/mccc2-p-ala430 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown