Is GBE1 p.Val485Ala (c.1454T>C) pathogenic?

GBE1 p.Val485Ala (c.1454T>C) is classified Uncertain significance in GBE1 (ClinVar, Single submitter, 1 submitter; last evaluated 2018-01-13). AlphaMissense: likely pathogenic (0.9575); Very rare (popmax 0.00685%, sas); Associated with glycogen storage disease due to glycogen branching enzyme deficiency.

How common is GBE1 p.Val485Ala (c.1454T>C) in the general population?

GBE1 p.Val485Ala (c.1454T>C) is very rare (popmax 0.00685%, sas) (gnomAD).

What do computational predictors say about GBE1 p.Val485Ala (c.1454T>C)?

AlphaMissense predicts likely pathogenic (score 0.9575) — an in-silico prediction, not a clinical call.

GBE1 p.Val485Ala

Q: What condition is associated with GBE1 p.Val485Ala (c.1454T>C)?

GBE1 p.Val485Ala (c.1454T>C) 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.1454T>C · rs771241994 · VCV901759

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9575 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00685%, sas)

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

glycogen storage disease due to glycogen branching enzyme deficiency

Computational evidence

Protein change
AlphaMissense	0.9575	likely pathogenic
REVEL	0.905	moderately pathogenic-leaning
SaProt	LLR -10.84	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 11	GERP 1.9, phastCons 1
Regional constraint	o/e 1.00	unconstrained · MANE · 271 kb · p 0.97 · regional, not allelic
Overall
CADD	25.3	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — a triage signal, not a reclassification

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00685% South Asian · 6/87,584 alleles

Filtering AF 0.00296% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00201%

Overall 0.000564% 9/1,595,656 alleles · very rare exomes 8/1,443,618 · genomes 1/152,038 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.00685%	14,597
Remaining individualsnot grpmax-eligible	0.00162%	61,888
African / African-American	0.00135%	74,304
European (non-Finnish)	8.54e-05%	1,171,272

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.Val485Ala
Coding: c.1454T>C
MANE Select: NM_000158
dbSNP: rs771241994
Type: single nucleotide variant
Location: chr3:81578089 (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

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-val485ala (accessed [today's date]).

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