Is MPI p.Pro130= (c.390C>T) pathogenic?

MPI p.Pro130= (c.390C>T) is classified Likely benign in MPI (ClinVar, Single submitter, 2 submitters; last evaluated 2024-01-29). Ultra-rare (popmax 0.0681%, sas); Associated with MPI-congenital disorder of glycosylation.

What condition is associated with MPI p.Pro130= (c.390C>T)?

MPI p.Pro130= (c.390C>T) is associated with MPI-congenital disorder of glycosylation (ClinVar).

How common is MPI p.Pro130= (c.390C>T) in the general population?

MPI p.Pro130= (c.390C>T) is ultra-rare (popmax 0.0681%, sas) (gnomAD).

How is MPI-CDG inherited?

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

MPI p.Pro130=

c.390C>T · rs140961968 · VCV703485

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0681%, 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 -14	GERP -4.5
Overall
CADD	0.829	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0681% South Asian · 62/91,090 alleles

Filtering AF 0.0544% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0495%

Overall 0.00873% 141/1,614,274 alleles · ultra-rare exomes 126/1,461,886 · genomes 15/152,388 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0681%	1,469
African / African-American	0.0346%	2,888
Remaining individualsnot grpmax-eligible	0.0304%	3,290
Admixed American	0.005%	20,011
European (non-Finnish)	0.00263%	38,066

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.Pro130=
Coding: c.390C>T
MANE Select: NM_002435
dbSNP: rs140961968
Type: single nucleotide variant
Location: chr15:74892705 (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.Pro130Leu Uncertain significance ★ ⚠ 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
MPI p.Arg219Gln 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-pro130 (accessed [today's date]).

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