Is GBE1 p.Asp24fs (c.70del) pathogenic?

GBE1 p.Asp24fs (c.70del) is classified Pathogenic/Likely pathogenic in GBE1 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2024-01-02). Very rare (popmax 0.00935%, afr); Associated with glycogen storage disease due to glycogen branching enzyme deficiency.

What condition is associated with GBE1 p.Asp24fs (c.70del)?

GBE1 p.Asp24fs (c.70del) is associated with glycogen storage disease due to glycogen branching enzyme deficiency (ClinVar).

How common is GBE1 p.Asp24fs (c.70del) in the general population?

GBE1 p.Asp24fs (c.70del) is very rare (popmax 0.00935%, afr) (gnomAD).

GBE1 p.Asp24fs

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.70del · rs1407149518 · VCV972014

Pathogenic/Likely pathogenic Multiple submitters

Classification

Pathogenic/Likely pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.00935%, 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.
Consequence	frameshift	predicted loss-of-function
NMD	predicted	premature termination codon in exon 1 of 16
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 4.6	GERP -1.6, phastCons 1
Overall
CADD	34.0	PHRED · no single calibrated threshold — expert panels disagree

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00935% African / African-American · 7/74,898 alleles

Filtering AF 0.00437% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00309%

Overall 0.000434% 7/1,613,486 alleles · very rare exomes 2/1,461,286 · genomes 5/152,200 · 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.Asp24fs
Coding: c.70del
MANE Select: NM_000158
dbSNP: rs1407149518
Type: Deletion
Location: chr3:81761448 (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.Asp24= Likely benign ★ 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.Arg156fs Pathogenic/Likely pathogenic ★★ same condition
GBE1 p.Arg468fs Pathogenic ★★ same condition
GBE1 p.Asp169fs 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-asp24fs (accessed [today's date]).

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