Is GBE1 p.Glu15= (c.45G>A) pathogenic?

GBE1 p.Glu15= (c.45G>A) is classified Conflicting classifications of pathogenicity in GBE1 (ClinVar, Conflicting submitters, 6 submitters; last evaluated 2026-01-20). Ultra-rare (popmax 0.0546%, afr); Associated with glycogen storage disease due to glycogen branching enzyme deficiency.

How common is GBE1 p.Glu15= (c.45G>A) in the general population?

GBE1 p.Glu15= (c.45G>A) is ultra-rare (popmax 0.0546%, afr) (gnomAD).

GBE1 p.Glu15=

Q: What condition is associated with GBE1 p.Glu15= (c.45G>A)?

GBE1 p.Glu15= (c.45G>A) is associated with glycogen storage disease due to glycogen branching enzyme deficiency, adult polyglucosan body disease (ClinVar).

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.45G>A · rs370326965 · VCV515221

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 6 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0546%, afr)

Conditions

glycogen storage disease due to glycogen branching enzyme deficiency

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -1.4	GERP -2.6
Overall
CADD	6.814	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0546% African / African-American · 41/75,042 alleles

Filtering AF 0.0413% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0367%

Overall 0.0098% 158/1,613,058 alleles · ultra-rare exomes 133/1,460,672 · genomes 25/152,386 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0546%	1,830
Middle Eastern	0.0337%	2,969
Remaining individualsnot grpmax-eligible	0.0176%	5,675
South Asian	0.0165%	6,070
Admixed American	0.00833%	11,998
European (non-Finnish)	0.00704%	14,212
East Asian	0.00223%	44,856

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.Glu15=
Coding: c.45G>A
MANE Select: NM_000158
dbSNP: rs370326965
Type: single nucleotide variant
Location: chr3:81761473 (GRCh38)
Gene constraint: LOEUF 1.211 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 96.30 · 3 PDB

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

Also linked: adult polyglucosan body disease

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 p.Glu15Lys Uncertain significance ★★ ⚠ same residue
GBE1 p.Glu15Ter Pathogenic ★ same residue
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

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-glu15 (accessed [today's date]).

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