Is MPI p.Ser67fs (c.199dup) pathogenic?

MPI p.Ser67fs (c.199dup) is classified Likely pathogenic in MPI (ClinVar, Single submitter, 1 submitter; last evaluated 2023-03-01). Absent from gnomAD; Associated with MPI-congenital disorder of glycosylation.

What condition is associated with MPI p.Ser67fs (c.199dup)?

MPI p.Ser67fs (c.199dup) is associated with MPI-congenital disorder of glycosylation (ClinVar).

How common is MPI p.Ser67fs (c.199dup) in the general population?

MPI p.Ser67fs (c.199dup) is absent from gnomAD (gnomAD).

How is MPI-CDG inherited?

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

MPI p.Ser67fs

c.199dup · rs2505813641 · VCV2501133

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Not reported

no gnomAD frequency available for this variant

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 3 of 8
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP -0.19	GERP -1.3

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

Population frequency

dbSNP / gnomAD

No gnomAD frequency available for this variant. This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: MPI
Protein: p.Ser67fs
Coding: c.199dup
MANE Select: NM_002435
dbSNP: rs2505813641
Type: Duplication
Location: chr15:74891432 (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.Arg56fs Pathogenic ★★ same condition
MPI p.Leu335fs Pathogenic/Likely pathogenic ★★ same condition
MPI p.Lys115Ter Pathogenic/Likely pathogenic ★★ same condition
MPI p.Val342fs Pathogenic/Likely pathogenic ★★ same condition
MPI p.Gln124fs Pathogenic ★ same condition
MPI p.Glu236fs Pathogenic ★ same condition
MPI p.Gly265fs Pathogenic ★ same condition
MPI p.His178fs 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-ser67fs (accessed [today's date]).

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