Is MPI p.Ala191= (c.573C>T) pathogenic?

MPI p.Ala191= (c.573C>T) is classified Conflicting classifications of pathogenicity in MPI (ClinVar, Conflicting submitters, 5 submitters; last evaluated 2025-12-31). Ultra-rare (popmax 0.0599%, nfe); Associated with MPI-congenital disorder of glycosylation.

What condition is associated with MPI p.Ala191= (c.573C>T)?

MPI p.Ala191= (c.573C>T) is associated with MPI-congenital disorder of glycosylation (ClinVar).

How common is MPI p.Ala191= (c.573C>T) in the general population?

MPI p.Ala191= (c.573C>T) is ultra-rare (popmax 0.0599%, nfe) (gnomAD).

How is MPI-CDG inherited?

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

MPI p.Ala191=

c.573C>T · rs200903491 · VCV706142

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 5 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0599%, nfe)

Conditions

MPI-congenital disorder of glycosylation

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation/SpliceAI carries the signal.
Splicing
SpliceAI	Δ0.21	acceptor gain · deltas
Constraint at this position
Conservation	phyloP -0.36	GERP -3.8, phastCons 0.004
Overall
CADD	13.83	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0599% European (non-Finnish) · 707/1,180,048 alleles

Filtering AF 0.0563% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0547%

Overall 0.0463% 747/1,614,090 alleles · ultra-rare exomes 715/1,461,878 · genomes 32/152,212 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.0599%	1,669
Admixed American	0.03%	3,334
Remaining individualsnot grpmax-eligible	0.0224%	4,463
African / African-American	0.00534%	18,730
Finnishnot grpmax-eligible	0.00468%	21,346
Ashkenazi Jewishnot grpmax-eligible	0.00338%	29,606

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.Ala191=
Coding: c.573C>T
MANE Select: NM_002435
dbSNP: rs200903491
Type: single nucleotide variant
Location: chr15:74893223 (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-ala191 (accessed [today's date]).

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