Is PYGL p.Val239fs (c.715_716del) pathogenic?

PYGL p.Val239fs (c.715716del) is classified Likely pathogenic in PYGL (ClinVar, Single submitter, 1 submitter). Ultra-rare (popmax 0.0165%, mid); Associated with glycogen storage disease VI.

What condition is associated with PYGL p.Val239fs (c.715_716del)?

PYGL p.Val239fs (c.715_716del) is associated with glycogen storage disease VI (ClinVar).

How common is PYGL p.Val239fs (c.715_716del) in the general population?

PYGL p.Val239fs (c.715_716del) is ultra-rare (popmax 0.0165%, mid) (gnomAD).

PYGL p.Val239fs

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.715_716del · rs750699019 · VCV2627506

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

ultra-rare (popmax 0.0165%, mid)

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 6 of 20
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 1.9	GERP -1.2, phastCons 1

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0165% Middle Eastern · 1/6,062 alleles

Filtering AF 0.000875% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000443%

Overall 0.00031% 5/1,614,234 alleles · ultra-rare exomes 5/1,461,876 · genomes 0/152,358 · joint denominator

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0165%	6,062
South Asian	0.00329%	30,362
European (non-Finnish)	8.47e-05%	1,180,032

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: PYGL
Protein: p.Val239fs
Coding: c.715_716del
MANE Select: NM_002863
dbSNP: rs750699019
Type: Deletion
Location: chr14:50921012 (GRCh38)
Gene constraint: LOEUF 1.048 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 92.87 · 19 PDB
Residue 239: a β-strand

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.Cys109fs Pathogenic ★ same condition
PYGL p.Leu381fs Likely pathogenic ★ same condition
PYGL p.Met100fs Pathogenic ★ same condition
PYGL p.Pro282fs 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-val239fs (accessed [today's date]).

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