Is GBE1 p.Arg156fs (c.466_470del) pathogenic?

GBE1 p.Arg156fs (c.466470del) is classified Pathogenic/Likely pathogenic in GBE1 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2024-03-06). Very rare (popmax 0.000595%, nfe); Associated with glycogen storage disease due to glycogen branching enzyme deficiency.

How common is GBE1 p.Arg156fs (c.466_470del) in the general population?

GBE1 p.Arg156fs (c.466_470del) is very rare (popmax 0.000595%, nfe) (gnomAD).

GBE1 p.Arg156fs

Q: What condition is associated with GBE1 p.Arg156fs (c.466_470del)?

GBE1 p.Arg156fs (c.466_470del) 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.466_470del · rs2107074878 · VCV1426965

Pathogenic/Likely pathogenic Multiple submitters

Classification

Pathogenic/Likely pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.000595%, nfe)

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.
Consequence	frameshift	predicted loss-of-function
NMD	predicted	premature termination codon in exon 4 of 16
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 5.2	GERP 1.9, phastCons 1

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.000595% European (non-Finnish) · 7/1,177,226 alleles

Filtering AF 0.000247% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000159%

Overall 0.000435% 7/1,610,588 alleles · very rare exomes 7/1,458,288 · genomes 0/152,300 · joint denominator

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.Arg156fs
Coding: c.466_470del
MANE Select: NM_000158
dbSNP: rs2107074878
Type: Deletion
Location: chr3:81649881 (GRCh38)
Gene constraint: LOEUF 1.211 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 96.30 · 3 PDB
Residue 156: a β-strand

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.Arg156His Uncertain significance ★★ same residue
GBE1 p.Arg156Cys Conflicting classifications of pathogenicity ★ ⚠ same residue
GBE1 c.1799_1803+8del Likely pathogenic ★★ same condition
GBE1 p.Ala16fs Pathogenic/Likely pathogenic ★★ same condition
GBE1 p.Ala9fs Pathogenic/Likely pathogenic ★★ same condition
GBE1 p.Arg468fs Pathogenic ★★ same condition
GBE1 p.Asp169fs Pathogenic/Likely pathogenic ★★ same condition
GBE1 p.Asp24fs 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-arg156fs (accessed [today's date]).

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