Is MPI p.Arg328Trp (c.982C>T) pathogenic?

MPI p.Arg328Trp (c.982C>T) is classified Benign/Likely benign in MPI (ClinVar, Multiple submitters, 10 submitters; last evaluated 2026-02-04). AlphaMissense: likely benign (0.0973); Low-frequency (popmax 1.21%, nfe); Associated with MPI-congenital disorder of glycosylation.

What condition is associated with MPI p.Arg328Trp (c.982C>T)?

MPI p.Arg328Trp (c.982C>T) is associated with MPI-congenital disorder of glycosylation (ClinVar).

How common is MPI p.Arg328Trp (c.982C>T) in the general population?

MPI p.Arg328Trp (c.982C>T) is low-frequency (popmax 1.21%, 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.Arg328Trp (c.982C>T)?

AlphaMissense predicts likely benign (score 0.0973) — an in-silico prediction, not a clinical call.

MPI p.Arg328Trp

c.982C>T · rs117089191 · VCV94072

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 10 submitters

AlphaMissense

likely benign

0.0973 · ACMG-weighted

gnomAD v4.1

Rare

low-frequency (popmax 1.21%, nfe)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

MPI-congenital disorder of glycosylation

Computational evidence

Protein change
AlphaMissense	0.0973	likely benign
REVEL	0.303	indeterminate
SaProt	LLR -10.53	damaging
⇒ SaProt calls this damaging; AlphaMissense does not; REVEL makes no call.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · C>G here scores Δ0.81 · evaluated, not missing
Constraint at this position
Conservation	phyloP -0.68	GERP -0.83
Regional constraint	o/e 0.98	unconstrained · MANE · 7,653 bp · p 0.66 · regional, not allelic
Overall
CADD	18.23	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 1.21% European (non-Finnish) · 14,231/1,180,024 alleles

Filtering AF 1.19% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.18%

Overall 0.94% 15,175/1,614,186 alleles · low-frequency

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	1.21%	83
Remaining individualsnot grpmax-eligible	0.813%	123
Finnishnot grpmax-eligible	0.373%	268
African / African-American	0.163%	615
Admixed American	0.113%	883
Middle Eastern	0.0165%	6,062
Ashkenazi Jewishnot grpmax-eligible	0.0135%	7,401
South Asian	0.0022%	45,543

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.Arg328Trp
Coding: c.982C>T
MANE Select: NM_002435
dbSNP: rs117089191
Type: single nucleotide variant
Location: chr15:74897148 (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.Arg328= Likely benign ★ 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-arg328trp (accessed [today's date]).

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