Is GBE1 p.Ser415fs (c.1241dup) pathogenic?

GBE1 p.Ser415fs (c.1241dup) is classified Likely pathogenic in GBE1 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-09-27). Associated with glycogen storage disease due to glycogen branching enzyme deficiency.

What condition is associated with GBE1 p.Ser415fs (c.1241dup)?

GBE1 p.Ser415fs (c.1241dup) is associated with glycogen storage disease due to glycogen branching enzyme deficiency (ClinVar).

GBE1 p.Ser415fs

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.1241dup · VCV4817833

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

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 10 of 16
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP -1.4	GERP -3.4

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

Variant & gene context

Gene: GBE1
Protein: p.Ser415fs
Coding: c.1241dup
MANE Select: NM_000158
Type: Duplication
Location: chr3:81586185 (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

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.Ser415Ter Likely pathogenic ★ same residue
GBE1 p.Ser415= Likely benign ★ same residue
GBE1 c.-35dup Benign ★★ same condition
GBE1 c.993-1dup Likely pathogenic ★ same condition
GBE1 p.Glu449fs Likely pathogenic ★ same condition
GBE1 p.Glu558Ter Likely pathogenic ★ same condition
GBE1 p.His312fs Likely pathogenic ★ same condition
GBE1 p.Leu117fs 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-ser415fs (accessed [today's date]).

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