Is PYGL p.Arg67fs (c.198del) pathogenic?

PYGL p.Arg67fs (c.198del) is classified Pathogenic in PYGL (ClinVar, Single submitter, 1 submitter; last evaluated 2022-11-21). No allele count reported in gnomAD v4.1 (AN 1,611,556); Associated with glycogen storage disease VI.

What condition is associated with PYGL p.Arg67fs (c.198del)?

PYGL p.Arg67fs (c.198del) is associated with glycogen storage disease VI (ClinVar).

How common is PYGL p.Arg67fs (c.198del) in the general population?

PYGL p.Arg67fs (c.198del) is no allele count reported in gnomAD v4.1 (AN 1,611,556) (gnomAD).

PYGL p.Arg67fs

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.198del · rs2502448999 · VCV1799523

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 1,611,556)

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 1 of 20
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 9.6	GERP 1.8, phastCons 1

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

Population frequency

gnomAD v4.1 · exomes + genomes

No allele count reported in gnomAD v4.1 (AN 1,611,556). 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: PYGL
Protein: p.Arg67fs
Coding: c.198del
MANE Select: NM_002863
dbSNP: rs2502448999
Type: Deletion
Location: chr14:50944206 (GRCh38)
Gene constraint: LOEUF 1.048 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 92.87 · 19 PDB
Residue 67: an α-helix

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.Cys109fs 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-arg67fs (accessed [today's date]).

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