Is MPDU1 p.Pro15Ser (c.43C>T) pathogenic?

MPDU1 p.Pro15Ser (c.43C>T) is classified Conflicting classifications of pathogenicity in MPDU1 (ClinVar, Conflicting submitters, 5 submitters; last evaluated 2025-06-12). AlphaMissense: likely benign (0.2576); Rare (popmax 0.421%, afr); Associated with MPDU1-congenital disorder of glycosylation.

What condition is associated with MPDU1 p.Pro15Ser (c.43C>T)?

MPDU1 p.Pro15Ser (c.43C>T) is associated with MPDU1-congenital disorder of glycosylation (ClinVar).

How common is MPDU1 p.Pro15Ser (c.43C>T) in the general population?

MPDU1 p.Pro15Ser (c.43C>T) is rare (popmax 0.421%, afr) (gnomAD).

How is MPDU1-CDG inherited?

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

What do computational predictors say about MPDU1 p.Pro15Ser (c.43C>T)?

AlphaMissense predicts likely benign (score 0.2576) — an in-silico prediction, not a clinical call.

MPDU1 p.Pro15Ser

c.43C>T · rs148935720 · VCV325513

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 5 submitters

AlphaMissense

likely benign

0.2576 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.421%, afr)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

MPDU1-congenital disorder of glycosylation

⚠ Built without this gene's context — gene constraint and dosage, protein structure, pathways, panels and related-variant links were not looked up for this page. why

Computational evidence

Protein change
AlphaMissense	0.2576	likely benign
REVEL	0.378	indeterminate
SaProt	LLR -2.36	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL makes no call.
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP 7.6	GERP 2.4, phastCons 1
Regional constraint	o/e 0.94	unconstrained · MANE · 3,685 bp · p 0.29 · regional, not allelic
Overall
CADD	21.9	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 0.421% African / African-American · 316/75,052 alleles

Filtering AF 0.383% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.368%

Overall 0.0208% 336/1,614,196 alleles · rare exomes 174/1,461,830 · genomes 162/152,366 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.421%	238
Remaining individualsnot grpmax-eligible	0.0256%	3,907
Admixed American	0.00666%	15,009

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: MPDU1
Protein: p.Pro15Ser
Coding: c.43C>T
MANE Select: NM_004870
dbSNP: rs148935720
Type: single nucleotide variant
Location: chr17:7583905 (GRCh38)

Full MPDU1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

MPDU1-congenital disorder of glycosylation — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For MPDU1-CDG (Orphanet):

Inheritance: Autosomal recessive
Onset: Infancy, Neonatal

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/mpdu1-p-pro15ser (accessed [today's date]).

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