Is MPI p.Ile249= (c.747C>A) pathogenic?

MPI p.Ile249= (c.747C>A) is classified Likely benign in MPI (ClinVar, Single submitter, 1 submitter; last evaluated 2020-08-01). Very rare (popmax 0.00134%, afr); Associated with MPI-congenital disorder of glycosylation.

What condition is associated with MPI p.Ile249= (c.747C>A)?

MPI p.Ile249= (c.747C>A) is associated with MPI-congenital disorder of glycosylation (ClinVar).

How common is MPI p.Ile249= (c.747C>A) in the general population?

MPI p.Ile249= (c.747C>A) is very rare (popmax 0.00134%, afr) (gnomAD).

How is MPI-CDG inherited?

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

MPI p.Ile249=

c.747C>A · rs778875616 · VCV1097229

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00134%, afr)

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 -20	GERP -4.9
Overall
CADD	1.244	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00134% African / African-American · 1/74,896 alleles

Filtering AF 6.8e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.9e-05%

Overall 0.000248% 4/1,614,022 alleles · very rare exomes 2/1,461,880 · genomes 2/152,142 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00134%	74,896
European (non-Finnish)	0.000254%	393,346

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.Ile249=
Coding: c.747C>A
MANE Select: NM_002435
dbSNP: rs778875616
Type: single nucleotide variant
Location: chr15:74896228 (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.Ile249Thr Uncertain significance ★ ⚠ same residue
MPI p.Ile249Val Uncertain significance ⚠ same residue
MPI p.Ile249fs Pathogenic ★ 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

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-ile249 (accessed [today's date]).

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