Is MPI p.Glu166fs (c.497_498del) pathogenic?

MPI p.Glu166fs (c.497498del) is classified Likely pathogenic in MPI (ClinVar, Multiple submitters, 3 submitters; last evaluated 2025-07-31). Very rare (popmax 0.00439%, sas); Associated with MPI-congenital disorder of glycosylation.

What condition is associated with MPI p.Glu166fs (c.497_498del)?

MPI p.Glu166fs (c.497_498del) is associated with MPI-congenital disorder of glycosylation (ClinVar).

How common is MPI p.Glu166fs (c.497_498del) in the general population?

MPI p.Glu166fs (c.497_498del) is very rare (popmax 0.00439%, sas) (gnomAD).

How is MPI-CDG inherited?

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

MPI p.Glu166fs

c.497_498del · rs2141200280 · VCV1339719

Likely pathogenic Multiple submitters

Classification

Likely pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.00439%, sas)

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 5 of 8
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP -13	GERP -4.6

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00439% South Asian · 4/91,072 alleles

Filtering AF 0.00143% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000891%

Overall 0.000274% 4/1,461,654 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.Glu166fs
Coding: c.497_498del
MANE Select: NM_002435
dbSNP: rs2141200280
Type: Deletion
Location: chr15:74893146 (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.Ala363fs Pathogenic/Likely pathogenic ★★ same condition
MPI p.Arg29fs Pathogenic/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-glu166fs (accessed [today's date]).

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