Is PYGM p.Ser809fs (c.2422_2423dup) pathogenic?

PYGM p.Ser809fs (c.24222423dup) is classified Likely pathogenic in PYGM (ClinVar, Single submitter, 1 submitter; last evaluated 2024-03-08). Very rare (popmax 0.0022%, sas); Associated with glycogen storage disease V.

What condition is associated with PYGM p.Ser809fs (c.2422_2423dup)?

PYGM p.Ser809fs (c.2422_2423dup) is associated with glycogen storage disease V (ClinVar).

How common is PYGM p.Ser809fs (c.2422_2423dup) in the general population?

PYGM p.Ser809fs (c.2422_2423dup) is very rare (popmax 0.0022%, sas) (gnomAD).

PYGM p.Ser809fs

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

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

c.2422_2423dup · VCV3600014

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.0022%, sas)

Conditions

glycogen storage disease V

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function
NMD	escapes	premature termination codon in the last exon (20 of 20) — the truncated protein is likely expressed. PVS1 input, not an applied code
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP -0.94	GERP -3.7

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0022% South Asian · 2/91,088 alleles

Filtering AF 0.000365% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000136%

Overall 0.000137% 2/1,461,890 alleles · very rare

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: PYGM
Protein: p.Ser809fs
Coding: c.2422_2423dup
MANE Select: NM_005609
Type: Duplication
Location: chr11:64746764 (GRCh38)
Gene constraint: LOEUF 0.962 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 94.41 · 1 PDB
Residue 809: a UniProt-annotated variant site (in gsd5)

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

Disease context

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

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

Inheritance: Autosomal recessive
Onset: Adolescent, Adult, Childhood

Similar variants

PYGM p.Ser809= Likely benign ★ same residue
PYGM p.Ala452fs Pathogenic ★★ same condition
PYGM p.Arg490fs Pathogenic/Likely pathogenic ★★ same condition
PYGM p.Asn168Ter Pathogenic/Likely pathogenic ★★ same condition
PYGM p.Asp284fs Likely pathogenic ★★ same condition
PYGM p.Leu137fs Likely pathogenic ★★ same condition
PYGM p.Lys10fs Pathogenic/Likely pathogenic ★★ same condition
PYGM p.Met351fs 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/pygm-p-ser809fs (accessed [today's date]).

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