Is MPI p.Pro4fs (c.9_10del) pathogenic?

MPI p.Pro4fs (c.910del) is classified Pathogenic in MPI (ClinVar, Single submitter, 1 submitter; last evaluated 2024-03-06). Very rare (popmax 0.000137%); Associated with MPI-congenital disorder of glycosylation.

What condition is associated with MPI p.Pro4fs (c.9_10del)?

MPI p.Pro4fs (c.9_10del) is associated with MPI-congenital disorder of glycosylation (ClinVar).

How common is MPI p.Pro4fs (c.9_10del) in the general population?

MPI p.Pro4fs (c.9_10del) is very rare (popmax 0.000137%) (gnomAD).

How is MPI-CDG inherited?

Typically Autosomal recessive (Orphanet). A genetic counselor can assess individual risk for a family.

MPI p.Pro4fs

c.9_10del · VCV3680466

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.000137%)

Conditions

MPI-congenital disorder of glycosylation

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 1 of 8
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 1	GERP -4.1

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.000137%

Overall 0.000137% 2/1,455,404 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.Pro4fs
Coding: c.9_10del
MANE Select: NM_002435
Type: Deletion
Location: chr15:74890081 (GRCh38)
Gene constraint: LOEUF 1.04 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 96.50

Full MPI gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

MPI-congenital disorder of glycosylation — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For MPI-CDG (Orphanet):

Inheritance: Autosomal recessive
Onset: Infancy, Neonatal

Similar variants

MPI p.Pro4Ser Conflicting classifications of pathogenicity ★ ⚠ same residue
MPI p.Pro4= Uncertain significance same residue
MPI c.845-2del Likely pathogenic ★★ same condition
MPI p.Ala277fs Pathogenic/Likely pathogenic ★★ same condition
MPI p.Ala363fs Pathogenic/Likely pathogenic ★★ same condition
MPI p.Arg29fs Pathogenic/Likely pathogenic ★★ same condition
MPI p.Glu166fs Likely pathogenic ★★ same condition
MPI p.Glu211fs 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-pro4fs (accessed [today's date]).

Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown