Is MPI p.Ala363fs (c.1087del) pathogenic?

MPI p.Ala363fs (c.1087del) is classified Pathogenic/Likely pathogenic in MPI (ClinVar, Multiple submitters, 4 submitters; last evaluated 2024-11-07). Very rare (popmax 0.000169%, nfe); Associated with MPI-congenital disorder of glycosylation.

What condition is associated with MPI p.Ala363fs (c.1087del)?

MPI p.Ala363fs (c.1087del) is associated with MPI-congenital disorder of glycosylation (ClinVar).

How common is MPI p.Ala363fs (c.1087del) in the general population?

MPI p.Ala363fs (c.1087del) is very rare (popmax 0.000169%, nfe) (gnomAD).

How is MPI-CDG inherited?

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

MPI p.Ala363fs

c.1087del · rs2141209567 · VCV1066557

Pathogenic/Likely pathogenic Multiple submitters

Classification

Pathogenic/Likely pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.000169%, nfe)

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	escapes	premature termination codon in the last exon (8 of 8) — the truncated protein is likely expressed. PVS1 input, not an applied code
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP -0.17	GERP -0.6

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.000169% European (non-Finnish) · 2/1,179,972 alleles

Filtering AF 2.8e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.1e-05%

Overall 0.000124% 2/1,614,118 alleles · very rare exomes 2/1,461,822 · genomes 0/152,296 · 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: MPI
Protein: p.Ala363fs
Coding: c.1087del
MANE Select: NM_002435
dbSNP: rs2141209567
Type: Deletion
Location: chr15:74897544 (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 c.845-2del Likely pathogenic ★★ same condition
MPI p.Ala277fs 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
MPI p.Glu331fs Pathogenic/Likely pathogenic ★★ same condition
MPI p.Ile220fs Pathogenic/Likely pathogenic ★★ same condition
MPI p.Ile40fs 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-ala363fs (accessed [today's date]).

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