Is GBE1 p.Leu464= (c.1392C>T) pathogenic?

GBE1 p.Leu464= (c.1392C>T) is classified Conflicting classifications of pathogenicity in GBE1 (ClinVar, Conflicting submitters, 5 submitters; last evaluated 2026-01-21). Ultra-rare (popmax 0.0764%, amr); Associated with glycogen storage disease due to glycogen branching enzyme deficiency.

How common is GBE1 p.Leu464= (c.1392C>T) in the general population?

GBE1 p.Leu464= (c.1392C>T) is ultra-rare (popmax 0.0764%, amr) (gnomAD).

GBE1 p.Leu464=

Q: What condition is associated with GBE1 p.Leu464= (c.1392C>T)?

GBE1 p.Leu464= (c.1392C>T) 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.1392C>T · rs563241317 · VCV346790

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 5 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0764%, amr)

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 -0.39	GERP -3.5, phastCons 0.004
Overall
CADD	0.718	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0764% Admixed American · 45/58,924 alleles

Filtering AF 0.0586% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0524%

Overall 0.00666% 107/1,607,272 alleles · ultra-rare exomes 99/1,455,426 · genomes 8/151,846 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.0764%	1,309
Middle Eastern	0.0331%	3,025
Remaining individualsnot grpmax-eligible	0.0145%	6,915
European (non-Finnish)	0.00433%	23,080

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.Leu464=
Coding: c.1392C>T
MANE Select: NM_000158
dbSNP: rs563241317
Type: single nucleotide variant
Location: chr3:81581219 (GRCh38)
Gene constraint: LOEUF 1.211 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 96.30 · 3 PDB
Residue 464: an α-helix

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 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
GBE1 c.1618+1G>A Pathogenic/Likely pathogenic ★★ same condition
GBE1 c.1803+2T>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-leu464 (accessed [today's date]).

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