Is GBE1 p.Arg47= (c.141C>T) pathogenic?

GBE1 p.Arg47= (c.141C>T) is classified Likely pathogenic in GBE1 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-12-08). Very rare (popmax 0.0011%, sas); Associated with glycogen storage disease due to glycogen branching enzyme deficiency.

What condition is associated with GBE1 p.Arg47= (c.141C>T)?

GBE1 p.Arg47= (c.141C>T) is associated with glycogen storage disease due to glycogen branching enzyme deficiency (ClinVar).

How common is GBE1 p.Arg47= (c.141C>T) in the general population?

GBE1 p.Arg47= (c.141C>T) is very rare (popmax 0.0011%, sas) (gnomAD).

GBE1 p.Arg47=

Q: How is Glycogen storage disease due to glycogen branching enzyme deficiency inherited?

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

c.141C>T · VCV4789826

Likely pathogenic Multiple submitters

Classification

Likely pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

very rare (popmax 0.0011%, sas)

Conditions

glycogen storage disease due to glycogen branching enzyme deficiency

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation/SpliceAI carries the signal.
Splicing
SpliceAI	Δ0.98	donor gain · deltas
Pangolin	Δ0.81	gain · loss 0.61 · agrees with SpliceAI · independent
Constraint at this position
Conservation	phyloP 5.7	GERP 1.4, phastCons 1
Overall
CADD	29.2	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0011% South Asian · 1/90,976 alleles

Filtering AF 0.000544% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00043%

Overall 0.000894% 13/1,454,934 alleles · very rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0011%	90,976
European (non-Finnish)	0.00102%	97,948

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: GBE1
Protein: p.Arg47=
Coding: c.141C>T
MANE Select: NM_000158
Type: single nucleotide variant
Location: chr3:81761377 (GRCh38)
Gene constraint: LOEUF 1.211 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 96.30 · 3 PDB
Residue 47: an α-helix

Full GBE1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

glycogen storage disease due to glycogen branching enzyme deficiency — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Glycogen storage disease due to glycogen branching enzyme deficiency (Orphanet):

Inheritance: Autosomal recessive
Onset: All ages
Prevalence: 1-9 / 1 000 000 (Worldwide)

Similar variants

GBE1 c.1109-1G>T Likely pathogenic ★★ same condition
GBE1 c.1236+1G>A Likely pathogenic ★★ same condition
GBE1 c.1336-1G>A Pathogenic/Likely pathogenic ★★ same condition
GBE1 c.143+1G>A Pathogenic ★★ same condition
GBE1 c.143+2T>C Pathogenic/Likely pathogenic ★★ same condition
GBE1 c.144-1G>C Pathogenic/Likely pathogenic ★★ same condition
GBE1 c.1618+1G>A Pathogenic/Likely pathogenic ★★ same condition
GBE1 c.1803+2T>C Pathogenic/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/gbe1-p-arg47 (accessed [today's date]).

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