Is PYGM p.Val503fs (c.1507del) pathogenic?

PYGM p.Val503fs (c.1507del) is classified Pathogenic/Likely pathogenic in PYGM (ClinVar, Multiple submitters, 3 submitters; last evaluated 2026-01-02). Very rare (popmax 0.00017%, nfe); Associated with glycogen storage disease V.

What condition is associated with PYGM p.Val503fs (c.1507del)?

PYGM p.Val503fs (c.1507del) is associated with glycogen storage disease V (ClinVar).

How common is PYGM p.Val503fs (c.1507del) in the general population?

PYGM p.Val503fs (c.1507del) is very rare (popmax 0.00017%, nfe) (gnomAD).

PYGM p.Val503fs

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.1507del · rs1272600960 · VCV1071212

Pathogenic/Likely pathogenic Multiple submitters

Classification

Pathogenic/Likely pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.00017%, nfe)

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	predicted	premature termination codon in exon 12 of 20
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 6.9	GERP 2, phastCons 1
Overall
CADD	32.0	PHRED · no single calibrated threshold — expert panels disagree

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00017% European (non-Finnish) · 2/1,178,062 alleles

Filtering AF 2.8e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.1e-05%

Overall 0.000124% 2/1,611,648 alleles · very rare exomes 1/1,459,674 · genomes 1/151,974 · joint denominator

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.Val503fs
Coding: c.1507del
MANE Select: NM_005609
dbSNP: rs1272600960
Type: Deletion
Location: chr11:64753084 (GRCh38)
Gene constraint: LOEUF 0.962 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 94.41 · 1 PDB
Residue 503: a UniProt-annotated variant site (in gsd5); an α-helix

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 c.2177_2177+3del Likely pathogenic ★★ same condition
PYGM p.Ala55fs Pathogenic ★★ same condition
PYGM p.Arg161_Tyr162insTer Pathogenic/Likely pathogenic ★★ same condition
PYGM p.Arg194fs Pathogenic/Likely pathogenic ★★ same condition
PYGM p.Asn454_Leu464del Pathogenic/Likely pathogenic ★★ same condition
PYGM p.Glu125fs Pathogenic ★★ same condition
PYGM p.Glu27fs Pathogenic ★★ same condition
PYGM p.Glu797fs 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-val503fs (accessed [today's date]).

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