MPI p.Pro275=
c.825C>T · VCV4057844
Uncertain significance
No assertion criteria
Classification
Uncertain significance
ClinVar
Review
No assertion criteria ☆☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 8.47e-05%, nfe)
Conditions
1
MPI-congenital disorder of glycosylation
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 0.58 | GERP -0.93, phastCons 1 |
| Overall | ||
| CADD | 7.144 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
8.47e-05%
European (non-Finnish) · 1/1,180,040 alleles
Overall
6.84e-05%
1/1,461,874 alleles · very rare
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
- MPI
- Protein
- p.Pro275=
- Coding
- c.825C>T
- MANE Select
- NM_002435
- Type
- single nucleotide variant
- Location
- chr15:74896306 (GRCh38)
- Gene constraint
- LOEUF 1.04 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 96.50
Disease context
MPI-congenital disorder of glycosylation — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatmentsFor MPI-CDG (Orphanet):
- Inheritance
- Autosomal recessive
- Onset
- Infancy, Neonatal
Similar variants
- MPI c.145-1G>C Likely pathogenic ★★ same condition
- MPI c.16+2T>C Likely pathogenic ★★ same condition
- MPI c.488-1G>C Pathogenic/Likely pathogenic ★★ same condition
- MPI c.488-2A>G Likely pathogenic ★★ same condition
- MPI c.844+1G>A Likely pathogenic ★★ same condition
- MPI c.845-2A>G Likely pathogenic ★★ same condition
- MPI p.Arg219Gln Pathogenic ★★ ⚠ same condition
- MPI p.Arg418His 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/mpi-p-pro275 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown