Is GBE1 p.Ser261Arg (c.783C>A) pathogenic?

GBE1 p.Ser261Arg (c.783C>A) is classified Likely pathogenic in GBE1 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-11-14). AlphaMissense: likely pathogenic (0.9692); No allele count reported in gnomAD v4.1 (AN 1,598,694); Associated with glycogen storage disease due to glycogen branching enzyme deficiency.

What condition is associated with GBE1 p.Ser261Arg (c.783C>A)?

GBE1 p.Ser261Arg (c.783C>A) is associated with glycogen storage disease due to glycogen branching enzyme deficiency (ClinVar).

How common is GBE1 p.Ser261Arg (c.783C>A) in the general population?

GBE1 p.Ser261Arg (c.783C>A) is no allele count reported in gnomAD v4.1 (AN 1,598,694) (gnomAD).

What do computational predictors say about GBE1 p.Ser261Arg (c.783C>A)?

AlphaMissense predicts likely pathogenic (score 0.9692) — an in-silico prediction, not a clinical call.

GBE1 p.Ser261Arg

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.783C>A · rs1559673607 · VCV2945833

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9692 · ACMG-weighted

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 1,598,694)

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

glycogen storage disease due to glycogen branching enzyme deficiency

Computational evidence

Protein change
AlphaMissense	0.9692	likely pathogenic ✓ concordant with ClinVar · top 7% in GBE1
REVEL	0.769	pathogenic-leaning
SaProt	LLR -13.88	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 2.1	GERP -0.86, phastCons 1
Regional constraint	o/e 1.00	unconstrained · MANE · 271 kb · p 0.97 · regional, not allelic
Overall
CADD	20.5	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

No allele count reported in gnomAD v4.1 (AN 1,598,694). This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: GBE1
Protein: p.Ser261Arg
Coding: c.783C>A
MANE Select: NM_000158
dbSNP: rs1559673607
Type: single nucleotide variant
Location: chr3:81642990 (GRCh38)
Gene constraint: LOEUF 1.211 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 96.30 · 3 PDB
Residue 261: 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

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-ser261arg (accessed [today's date]).

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