Is MPI p.Ser380fs (c.1137_1140del) pathogenic?

MPI p.Ser380fs (c.11371140del) is classified Pathogenic in MPI (ClinVar, Single submitter, 1 submitter; last evaluated 2022-03-12). Very rare (popmax 0.00223%, eas); Associated with MPI-congenital disorder of glycosylation.

What condition is associated with MPI p.Ser380fs (c.1137_1140del)?

MPI p.Ser380fs (c.1137_1140del) is associated with MPI-congenital disorder of glycosylation (ClinVar).

How common is MPI p.Ser380fs (c.1137_1140del) in the general population?

MPI p.Ser380fs (c.1137_1140del) is very rare (popmax 0.00223%, eas) (gnomAD).

How is MPI-CDG inherited?

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

MPI p.Ser380fs

c.1137_1140del · rs1373861722 · VCV2109971

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.00223%, eas)

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 1.4	GERP -0.69, phastCons 1
Overall
CADD	34.0	PHRED · no single calibrated threshold — expert panels disagree

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00223% East Asian · 1/44,890 alleles

Overall 6.2e-05% 1/1,614,034 alleles · very rare exomes 0/1,461,884 · genomes 1/152,150 · 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.Ser380fs
Coding: c.1137_1140del
MANE Select: NM_002435
dbSNP: rs1373861722
Type: Deletion
Location: chr15:74897592 (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.Ser380Asn Uncertain significance ★ ⚠ same residue
MPI p.Ser380= Likely benign ★ 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-ser380fs (accessed [today's date]).

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