Is MPI p.Ser380= (c.1140C>T) pathogenic?

MPI p.Ser380= (c.1140C>T) is classified Likely benign in MPI (ClinVar, Single submitter, 1 submitter; last evaluated 2021-10-03). Very rare (popmax 0.0011%, sas); Associated with MPI-congenital disorder of glycosylation.

What condition is associated with MPI p.Ser380= (c.1140C>T)?

MPI p.Ser380= (c.1140C>T) is associated with MPI-congenital disorder of glycosylation (ClinVar).

How common is MPI p.Ser380= (c.1140C>T) in the general population?

MPI p.Ser380= (c.1140C>T) is very rare (popmax 0.0011%, sas) (gnomAD).

How is MPI-CDG inherited?

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

MPI p.Ser380=

c.1140C>T · rs2141209705 · VCV1147646

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.0011%, sas)

Conditions

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 0.63	GERP 2.5, phastCons 0.69
Overall
CADD	9.158	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0011% South Asian · 1/91,084 alleles

Overall 6.19e-05% 1/1,614,228 alleles · very rare exomes 1/1,461,882 · genomes 0/152,346 · 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.Ser380=
Coding: c.1140C>T
MANE Select: NM_002435
dbSNP: rs2141209705
Type: single nucleotide variant
Location: chr15:74897598 (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.Ser380fs Pathogenic ★ same residue
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

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-ser380 (accessed [today's date]).

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