MCCC1 p.Pro253fs
c.756_757del · VCV4773180
Pathogenic
Single submitter
Classification
Pathogenic
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
Consequence
frameshift
predicted LoF
gnomAD v4.1
Rare
Conditions
1
3-methylcrotonyl-CoA carboxylase 1 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 7 of 19 |
| Splicing | ||
| SpliceAI | — | not assessed · substitutions only |
| Constraint at this position | ||
| Conservation | phyloP 12 | GERP 2, phastCons 1 |
Predicted loss-of-function is descriptive, not an applied PVS1 code.
Variant & gene context
- Gene
- MCCC1
- Protein
- p.Pro253fs
- Coding
- c.756_757del
- MANE Select
- NM_020166
- Type
- Microsatellite
- Location
- chr3:183071003 (GRCh38)
- Gene constraint
- LOEUF 0.819 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 87.53 · 14 PDB
- Residue 253
- the biotin carboxylation domain; the atp-grasp domain
Disease context
3-methylcrotonyl-CoA carboxylase 1 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
- MCCC1 p.Pro253Leu Conflicting classifications of pathogenicity ★ ⚠ same residue
- MCCC1 p.Pro253= Likely benign ★ same residue
- MCCC1 p.Glu234fs Likely pathogenic ★★ same condition
- MCCC1 p.Gly58fs Pathogenic/Likely pathogenic ★★ same condition
- MCCC1 p.Leu377fs Pathogenic/Likely pathogenic ★★ same condition
- MCCC1 p.Lys284del Likely pathogenic ★★ same condition
- MCCC1 p.Lys556fs Pathogenic/Likely pathogenic ★★ same condition
- MCCC1 p.Val398fs 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/mccc1-p-pro253fs (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown