Is MPI p.Arg152Gln (c.455G>A) pathogenic?

MPI p.Arg152Gln (c.455G>A) is classified Conflicting classifications of pathogenicity in MPI (ClinVar, Conflicting submitters, 2 submitters; last evaluated 2024-01-16). AlphaMissense: ambiguous (0.3801); Very rare (popmax 0.00153%, nfe); Associated with MPI-congenital disorder of glycosylation.

What condition is associated with MPI p.Arg152Gln (c.455G>A)?

MPI p.Arg152Gln (c.455G>A) is associated with MPI-congenital disorder of glycosylation (ClinVar).

How common is MPI p.Arg152Gln (c.455G>A) in the general population?

MPI p.Arg152Gln (c.455G>A) is very rare (popmax 0.00153%, nfe) (gnomAD).

How is MPI-CDG inherited?

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

What do computational predictors say about MPI p.Arg152Gln (c.455G>A)?

AlphaMissense predicts ambiguous (score 0.3801) — an in-silico prediction, not a clinical call.

MPI p.Arg152Gln

c.455G>A · rs766458792 · VCV2503985

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 2 submitters

AlphaMissense

ambiguous

0.3801 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00153%, nfe)

Missense predictors

2/2 damaging

REVEL, SaProt · AlphaMissense indeterminate

Conditions

MPI-congenital disorder of glycosylation

Computational evidence

Protein change
AlphaMissense	0.3801	ambiguous
REVEL	0.937	strongly pathogenic-leaning
SaProt	LLR -11.97	damaging
⇒ REVEL and SaProt both call this damaging; AlphaMissense is indeterminate.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 2.4, phastCons 1
Regional constraint	o/e 0.98	unconstrained · MANE · 7,653 bp · p 0.66 · regional, not allelic
Overall
CADD	33.0	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00153% European (non-Finnish) · 18/1,180,054 alleles

Filtering AF 0.000953% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000787%

Overall 0.00124% 20/1,614,144 alleles · very rare exomes 19/1,461,890 · genomes 1/152,254 · joint denominator

Ancestry group	Frequency	1 in
Remaining individualsnot grpmax-eligible	0.0016%	62,490
European (non-Finnish)grpmax	0.00153%	65,559
South Asian	0.0011%	91,094

Remaining individuals shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Arg152Gln
Coding: c.455G>A
MANE Select: NM_002435
dbSNP: rs766458792
Type: single nucleotide variant
Location: chr15:74892770 (GRCh38)
Gene constraint: LOEUF 1.04 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 96.50
Residue 152: a UniProt-annotated variant site (in cdg1b)

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.Arg152Pro Uncertain significance ★ ⚠ same residue
MPI p.Arg152Leu Uncertain significance ★ ⚠ same residue
MPI p.Arg152Trp 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

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-arg152gln (accessed [today's date]).

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