Is MPI p.Arg5Ter (c.13C>T) pathogenic?

MPI p.Arg5Ter (c.13C>T) is classified Pathogenic/Likely pathogenic in MPI (ClinVar, Multiple submitters, 4 submitters; last evaluated 2025-12-05). Very rare (popmax 0.00223%, eas); Associated with MPI-congenital disorder of glycosylation.

What condition is associated with MPI p.Arg5Ter (c.13C>T)?

MPI p.Arg5Ter (c.13C>T) is associated with MPI-congenital disorder of glycosylation (ClinVar).

How common is MPI p.Arg5Ter (c.13C>T) in the general population?

MPI p.Arg5Ter (c.13C>T) is very rare (popmax 0.00223%, eas) (gnomAD).

How is MPI-CDG inherited?

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

MPI p.Arg5Ter

c.13C>T · rs1452559752 · VCV554184

Pathogenic/Likely pathogenic Multiple submitters

Classification

Pathogenic/Likely pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

Consequence

nonsense (stop-gain)

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.00223%, eas)

Conditions

MPI-congenital disorder of glycosylation

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	nonsense (stop-gain)	predicted loss-of-function
NMD	predicted	premature termination codon in exon 1 of 8
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.028	GERP -4.1
Overall
CADD	26.1	PHRED · no single calibrated threshold — expert panels disagree

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00223% East Asian · 1/44,880 alleles

Filtering AF 0.000359% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00026%

Overall 0.000684% 11/1,607,920 alleles · very rare exomes 10/1,455,740 · genomes 1/152,180 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00223%	44,880
South Asian	0.0011%	91,072
European (non-Finnish)	0.000763%	131,109

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.Arg5Ter
Coding: c.13C>T
MANE Select: NM_002435
dbSNP: rs1452559752
Type: single nucleotide variant
Location: chr15:74890086 (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.Arg5= Uncertain significance same residue
MPI p.Arg5Leu 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

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-arg5ter (accessed [today's date]).

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