Is MPI p.Cys283= (c.849C>T) pathogenic?

MPI p.Cys283= (c.849C>T) is classified Conflicting classifications of pathogenicity in MPI (ClinVar, Conflicting submitters, 2 submitters; last evaluated 2026-01-22). Ultra-rare (popmax 0.0133%, amr); Associated with MPI-congenital disorder of glycosylation.

What condition is associated with MPI p.Cys283= (c.849C>T)?

MPI p.Cys283= (c.849C>T) is associated with MPI-congenital disorder of glycosylation (ClinVar).

How common is MPI p.Cys283= (c.849C>T) in the general population?

MPI p.Cys283= (c.849C>T) is ultra-rare (popmax 0.0133%, amr) (gnomAD).

How is MPI-CDG inherited?

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

MPI p.Cys283=

c.849C>T · rs377419930 · VCV755362

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0133%, amr)

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 -8.6	GERP -4.8
Overall
CADD	1.495	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0133% Admixed American · 8/60,002 alleles

Filtering AF 0.0079% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00736%

Overall 0.00812% 131/1,613,970 alleles · ultra-rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.0133%	7,500
Remaining individualsnot grpmax-eligible	0.0112%	8,926
European (non-Finnish)	0.00932%	10,727
African / African-American	0.00534%	18,723
South Asian	0.0022%	45,547

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.Cys283=
Coding: c.849C>T
MANE Select: NM_002435
dbSNP: rs377419930
Type: single nucleotide variant
Location: chr15:74897015 (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.Cys283Trp 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-cys283 (accessed [today's date]).

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