Is MPI p.Arg56Gln (c.167G>A) pathogenic?

MPI p.Arg56Gln (c.167G>A) is classified Uncertain significance in MPI (ClinVar, Multiple submitters, 3 submitters; last evaluated 2022-03-09). AlphaMissense: likely benign (0.1082); Ultra-rare (popmax 0.0183%, amr); Associated with MPI-congenital disorder of glycosylation.

What condition is associated with MPI p.Arg56Gln (c.167G>A)?

MPI p.Arg56Gln (c.167G>A) is associated with MPI-congenital disorder of glycosylation (ClinVar).

How common is MPI p.Arg56Gln (c.167G>A) in the general population?

MPI p.Arg56Gln (c.167G>A) is ultra-rare (popmax 0.0183%, amr) (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.Arg56Gln (c.167G>A)?

AlphaMissense predicts likely benign (score 0.1082) — an in-silico prediction, not a clinical call.

MPI p.Arg56Gln

c.167G>A · rs200452019 · VCV966402

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

AlphaMissense

likely benign

0.1082 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0183%, amr)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

MPI-congenital disorder of glycosylation

Computational evidence

Protein change
AlphaMissense	0.1082	likely benign
REVEL	0.472	indeterminate
SaProt	LLR -8.69	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL makes no call.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · G>T here scores Δ0.44 · evaluated, not missing
Constraint at this position
Conservation	phyloP 8.6	GERP 1.1, phastCons 1
Regional constraint	o/e 0.98	unconstrained · MANE · 7,653 bp · p 0.66 · regional, not allelic
Overall
CADD	24.8	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0183% Admixed American · 11/60,012 alleles

Filtering AF 0.0155% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0148%

Overall 0.0142% 230/1,614,122 alleles · ultra-rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.0183%	5,456
European (non-Finnish)	0.0175%	5,701
Remaining individualsnot grpmax-eligible	0.0128%	7,813
Finnishnot grpmax-eligible	0.00312%	32,011
African / African-American	0.00133%	75,022
South Asian	0.0011%	91,078

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.Arg56Gln
Coding: c.167G>A
MANE Select: NM_002435
dbSNP: rs200452019
Type: single nucleotide variant
Location: chr15:74891401 (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.Arg56Ter Pathogenic/Likely pathogenic ★★ same residue
MPI p.Arg56fs 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
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-arg56gln (accessed [today's date]).

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