Is MPI p.Leu101= (c.303C>T) pathogenic?

MPI p.Leu101= (c.303C>T) is classified Conflicting classifications of pathogenicity in MPI (ClinVar, Conflicting submitters, 10 submitters; last evaluated 2026-01-26). Rare (popmax 0.446%, nfe); Associated with MPI-congenital disorder of glycosylation.

What condition is associated with MPI p.Leu101= (c.303C>T)?

MPI p.Leu101= (c.303C>T) is associated with MPI-congenital disorder of glycosylation (ClinVar).

How common is MPI p.Leu101= (c.303C>T) in the general population?

MPI p.Leu101= (c.303C>T) is rare (popmax 0.446%, nfe) (gnomAD).

How is MPI-CDG inherited?

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

MPI p.Leu101=

c.303C>T · rs139228075 · VCV196348

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 10 submitters

gnomAD v4.1

Rare

rare (popmax 0.446%, nfe)

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 -3.4	GERP -4.3
Overall
CADD	4.515	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.446% European (non-Finnish) · 5,266/1,180,028 alleles

Filtering AF 0.436% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.432%

Overall 0.349% 5,633/1,614,188 alleles · rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.446%	224
Admixed American	0.268%	373
Remaining individualsnot grpmax-eligible	0.229%	437
African / African-American	0.0679%	1,472
Finnishnot grpmax-eligible	0.0125%	8,005
Ashkenazi Jewishnot grpmax-eligible	0.00675%	14,804
South Asian	0.0022%	45,540

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.Leu101=
Coding: c.303C>T
MANE Select: NM_002435
dbSNP: rs139228075
Type: single nucleotide variant
Location: chr15:74891537 (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.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
MPI p.Arg219Gln Pathogenic ★★ ⚠ same condition
MPI p.Arg418His 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-leu101 (accessed [today's date]).

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