Is MPI p.Arg152Trp (c.454C>T) pathogenic?

MPI p.Arg152Trp (c.454C>T) is classified Uncertain significance in MPI (ClinVar, Single submitter, 1 submitter; last evaluated 2025-09-18). AlphaMissense: likely pathogenic (0.7273); Ultra-rare (popmax 0.0178%, eas); Associated with Inborn genetic diseases.

What condition is associated with MPI p.Arg152Trp (c.454C>T)?

MPI p.Arg152Trp (c.454C>T) is associated with Inborn genetic diseases (ClinVar).

How common is MPI p.Arg152Trp (c.454C>T) in the general population?

MPI p.Arg152Trp (c.454C>T) is ultra-rare (popmax 0.0178%, eas) (gnomAD).

What do computational predictors say about MPI p.Arg152Trp (c.454C>T)?

AlphaMissense predicts likely pathogenic (score 0.7273) — an in-silico prediction, not a clinical call.

MPI p.Arg152Trp

c.454C>T · VCV4625192

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.7273 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0178%, eas)

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.7273	likely pathogenic
REVEL	0.964	strongly pathogenic-leaning
SaProt	LLR -14.70	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 4.8	GERP 1.3, phastCons 1
Regional constraint	o/e 0.98	unconstrained · MANE · 7,653 bp · p 0.66 · regional, not allelic
Overall
CADD	31.0	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — 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 0.0178% East Asian · 8/44,900 alleles

Filtering AF 0.00883% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00641%

Overall 0.000867% 14/1,614,114 alleles · ultra-rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.0178%	5,612
Finnishnot grpmax-eligible	0.00312%	32,018
European (non-Finnish)	0.000339%	295,012

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.Arg152Trp
Coding: c.454C>T
MANE Select: NM_002435
Type: single nucleotide variant
Location: chr15:74892769 (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

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

MPI p.Arg152Gln Conflicting classifications of pathogenicity ★ ⚠ same residue
MPI p.Arg152Leu Uncertain significance ★ ⚠ same residue
MPI p.Arg152Pro Uncertain significance ★ ⚠ same residue
MPI p.Asn273Ser Uncertain significance ★★ ⚠ same condition
MPI p.Asp80Asn Uncertain significance ★★ ⚠ same condition
MPI p.Glu331Ala Uncertain significance ★★ ⚠ same condition
MPI p.Lys360Arg Uncertain significance ★★ ⚠ same condition
MPI p.Pro326Ser Uncertain significance ★★ ⚠ 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-arg152trp (accessed [today's date]).

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