Is PYGL p.Cys109fs (c.324del) pathogenic?

PYGL p.Cys109fs (c.324del) is classified Pathogenic in PYGL (ClinVar, Single submitter, 1 submitter; last evaluated 2024-12-16). Associated with glycogen storage disease VI.

What condition is associated with PYGL p.Cys109fs (c.324del)?

PYGL p.Cys109fs (c.324del) is associated with glycogen storage disease VI (ClinVar).

PYGL p.Cys109fs

Q: How is Glycogen storage disease due to liver glycogen phosphorylase deficiency inherited?

Typically Autosomal recessive (Orphanet). A genetic counselor can assess individual risk for a family.

c.324del · VCV3727125

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

Conditions

glycogen storage disease VI

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 2 of 20
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 11	GERP 1.9, phastCons 1

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

Variant & gene context

Gene: PYGL
Protein: p.Cys109fs
Coding: c.324del
MANE Select: NM_002863
Type: Deletion
Location: chr14:50937757 (GRCh38)
Gene constraint: LOEUF 1.048 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 92.87 · 19 PDB
Residue 109: an α-helix; a functional site (involved in the association of subunits)

Full PYGL gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

glycogen storage disease VI — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Glycogen storage disease due to liver glycogen phosphorylase deficiency (Orphanet):

Inheritance: Autosomal recessive
Onset: Childhood

Similar variants

PYGL c.1828-2del Benign ★★ same condition
PYGL c.855+14del Likely benign ★★ same condition
PYGL c.*11del Benign ★★ same condition
PYGL p.Arg67fs Pathogenic ★ same condition
PYGL p.Leu381fs Likely pathogenic ★ same condition
PYGL p.Met100fs Pathogenic ★ same condition
PYGL p.Pro282fs Likely pathogenic ★ same condition
PYGL p.Val239fs 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/pygl-p-cys109fs (accessed [today's date]).

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