Is MPDU1 p.Glu4= (c.12G>A) pathogenic?

MPDU1 p.Glu4= (c.12G>A) is classified Likely benign in MPDU1 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-10-02). Ultra-rare (popmax 0.0329%, mid); Associated with MPDU1-congenital disorder of glycosylation.

What condition is associated with MPDU1 p.Glu4= (c.12G>A)?

MPDU1 p.Glu4= (c.12G>A) is associated with MPDU1-congenital disorder of glycosylation (ClinVar).

How common is MPDU1 p.Glu4= (c.12G>A) in the general population?

MPDU1 p.Glu4= (c.12G>A) is ultra-rare (popmax 0.0329%, mid) (gnomAD).

How is MPDU1-CDG inherited?

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

MPDU1 p.Glu4=

c.12G>A · rs146631664 · VCV389197

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0329%, mid)

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
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP 0.52	GERP -0.87, phastCons 0.019
Overall
CADD	7.698	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0329% Middle Eastern · 2/6,084 alleles

Filtering AF 0.0058% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00241%

Overall 0.00322% 52/1,613,984 alleles · ultra-rare exomes 43/1,461,720 · genomes 9/152,264 · joint denominator

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0329%	3,042
Remaining individualsnot grpmax-eligible	0.0096%	10,415
European (non-Finnish)	0.00347%	28,782
South Asian	0.0022%	45,544
Admixed American	0.00167%	60,016

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.Glu4=
Coding: c.12G>A
MANE Select: NM_004870
dbSNP: rs146631664
Type: single nucleotide variant
Location: chr17:7583874 (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-glu4 (accessed [today's date]).

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