MMUT p.Pro424=
c.1272T>C · rs2127417901 · VCV1155439
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.00133%, afr)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Splicing | ||
| SpliceAI | <0.2 | no splice effect predicted · four deltas, not one · how we know |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP -0.14 | GERP -5.2, phastCons 0.009 |
| Overall | ||
| CADD | 5.589 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00133%
African / African-American · 1/75,042 alleles
Overall
6.2e-05%
1/1,614,112 alleles · very rare
exomes 1/1,461,804 · genomes 0/152,308 · joint denominator
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
- MMUT
- Protein
- p.Pro424=
- Coding
- c.1272T>C
- MANE Select
- NM_000255
- dbSNP
- rs2127417901
- Type
- single nucleotide variant
- Location
- chr6:49451526 (GRCh38)
- Gene constraint
- LOEUF 1.18 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 92.72 · 6 PDB
- Residue 424
- a UniProt-annotated variant site (in mamm; mut0; decreased protein abundance; decreased methylmalonyl-coa mutase activity); a UniProt-annotated variant site (in mamm; mut-); a turn; a UniProt-annotated variant site (in mamm; mut0)
Similar variants
- MMUT p.Pro424Leu Pathogenic ★★ same residue
- MMUT p.Pro424Ser Uncertain significance ★ ⚠ same residue
- MMUT c.1083+2T>A Pathogenic ★★ same type
- MMUT c.1084-10A>G Pathogenic/Likely pathogenic ★★ same type
- MMUT c.1084-2A>G Pathogenic/Likely pathogenic ★★ same type
- MMUT c.1445-2A>G Pathogenic/Likely pathogenic ★★ same type
- MMUT c.1560+1G>T Pathogenic ★★ same type
- MMUT c.1677-1G>A 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/mmut-p-pro424 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown