Is GBE1 p.Lys193= (c.579G>A) pathogenic?

GBE1 p.Lys193= (c.579G>A) is classified Benign in GBE1 (ClinVar, Multiple submitters, 10 submitters; last evaluated 2026-02-04). Common (popmax 22.5%, afr) — too common for a highly-penetrant pathogenic allele; Associated with glycogen storage disease due to glycogen branching enzyme deficiency.

GBE1 p.Lys193=

Q: What condition is associated with GBE1 p.Lys193= (c.579G>A)?

GBE1 p.Lys193= (c.579G>A) is associated with glycogen storage disease due to glycogen branching enzyme deficiency, adult polyglucosan body disease (ClinVar).

Q: How common is GBE1 p.Lys193= (c.579G>A) in the general population?

GBE1 p.Lys193= (c.579G>A) is common (popmax 22.5%, afr) — too common for a highly-penetrant pathogenic allele (gnomAD).

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.579G>A · rs17019144 · VCV255390

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 10 submitters

gnomAD v4.1

Common

common (popmax 22.5%, afr) — too common for a highly-penetrant pathogenic allele

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 0.13	GERP 1.1, phastCons 0.94
Overall
CADD	8.086	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 22.5% African / African-American · 16,547/73,484 alleles

Filtering AF 22.2% ClinGen BA1/BS1 input FAF95, joint · FAF99 22.1%

Overall 4.18% 66,235/1,584,236 alleles · common exomes 52,651/1,432,126 · genomes 13,584/152,110 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	22.5%	4
East Asian	8.5%	12
Middle Eastern	6.97%	14
Admixed American	6.89%	15
South Asian	5.48%	18
Remaining individualsnot grpmax-eligible	4.81%	21
Amishnot grpmax-eligible	3.73%	27
Ashkenazi Jewishnot grpmax-eligible	2.82%	35
European (non-Finnish)	2.8%	36
Finnishnot grpmax-eligible	0.799%	125

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.Lys193=
Coding: c.579G>A
MANE Select: NM_000158
dbSNP: rs17019144
Type: single nucleotide variant
Location: chr3:81648968 (GRCh38)
Gene constraint: LOEUF 1.211 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 96.30 · 3 PDB
Residue 193: 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-lys193 (accessed [today's date]).

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