Is GBE1 p.Ser671fs (c.2011del) pathogenic?

GBE1 p.Ser671fs (c.2011del) is classified Pathogenic in GBE1 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-10-22). Very rare (popmax 8.49e-05%, nfe); Associated with Glycogen storage disease IV, classic hepatic.

What condition is associated with GBE1 p.Ser671fs (c.2011del)?

GBE1 p.Ser671fs (c.2011del) is associated with Glycogen storage disease IV, classic hepatic, glycogen storage disease due to glycogen branching enzyme deficiency (ClinVar).

How common is GBE1 p.Ser671fs (c.2011del) in the general population?

GBE1 p.Ser671fs (c.2011del) is very rare (popmax 8.49e-05%, nfe) (gnomAD).

GBE1 p.Ser671fs

c.2011del · rs780374709 · VCV1977757

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 8.49e-05%, nfe)

Conditions

Glycogen storage disease IV, classic hepatic

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function
NMD	escapes	premature termination codon within the last 50 nt of the penultimate exon (15 of 16, 41 nt from its 3' end) — the truncated protein is likely expressed. PVS1 input, not an applied code
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 12	GERP 2.3, phastCons 1

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 8.49e-05% European (non-Finnish) · 1/1,178,296 alleles

Overall 6.21e-05% 1/1,611,182 alleles · very rare exomes 1/1,458,978 · genomes 0/152,204 · 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.Ser671fs
Coding: c.2011del
MANE Select: NM_000158
dbSNP: rs780374709
Type: Deletion
Location: chr3:81499151 (GRCh38)
Gene constraint: LOEUF 1.211 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 96.30 · 3 PDB
Residue 671: a β-strand

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

Disease context

Glycogen storage disease IV, classic hepatic — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: glycogen storage disease due to glycogen branching enzyme deficiency

Similar variants

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.Arg156fs 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
GBE1 p.Asp413fs 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-ser671fs (accessed [today's date]).

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