MCCC2 p.Lys326fs
c.973del · VCV4816110
Likely pathogenic
Single submitter
Classification
Likely pathogenic
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
Consequence
frameshift
predicted LoF
gnomAD v4.1
Rare
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. | ||
| Consequence | frameshift | predicted loss-of-function |
|---|---|---|
| NMD | predicted | premature termination codon in exon 10 of 17 |
| Splicing | ||
| SpliceAI | — | not assessed · substitutions only |
| Constraint at this position | ||
| Conservation | phyloP 11 | GERP 1.7, phastCons 1 |
Predicted loss-of-function is descriptive, not an applied PVS1 code.
Variant & gene context
- Gene
- MCCC2
- Protein
- p.Lys326fs
- Coding
- c.973del
- MANE Select
- NM_022132
- Type
- Deletion
- Location
- chr5:71635219 (GRCh38)
- Gene constraint
- LOEUF 0.832 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 94.82 · 14 PDB
- Residue 326
- a β-strand; 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.1151del Likely pathogenic ★★ same condition
- MCCC2 c.281+1del Likely pathogenic ★★ same condition
- MCCC2 c.383+2del Likely pathogenic ★★ same condition
- MCCC2 c.739del Pathogenic/Likely pathogenic ★★ same condition
- MCCC2 p.Asn230fs Pathogenic/Likely pathogenic ★★ same condition
- MCCC2 p.Gly118del Pathogenic/Likely pathogenic ★★ same condition
- MCCC2 p.Gly368fs Pathogenic/Likely pathogenic ★★ same condition
- MCCC2 p.Gly79fs 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/mccc2-p-lys326fs (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown