Is PYGL p.Asp528= (c.1584T>C) pathogenic?

PYGL p.Asp528= (c.1584T>C) is classified Likely benign in PYGL (ClinVar, Multiple submitters, 2 submitters; last evaluated 2026-02-01). Ultra-rare (popmax 0.0657%, mid); Associated with glycogen storage disease VI.

What condition is associated with PYGL p.Asp528= (c.1584T>C)?

PYGL p.Asp528= (c.1584T>C) is associated with glycogen storage disease VI (ClinVar).

How common is PYGL p.Asp528= (c.1584T>C) in the general population?

PYGL p.Asp528= (c.1584T>C) is ultra-rare (popmax 0.0657%, mid) (gnomAD).

PYGL p.Asp528=

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.1584T>C · VCV3648110

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0657%, mid)

Conditions

glycogen storage disease VI

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP -6	GERP -3.1
Overall
CADD	0.115	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0657% Middle Eastern · 4/6,084 alleles

Filtering AF 0.0224% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0135%

Overall 0.00613% 99/1,613,888 alleles · ultra-rare exomes 90/1,461,682 · genomes 9/152,206 · joint denominator

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0657%	1,521
European (non-Finnish)	0.0072%	13,881
East Asian	0.00668%	14,963
Admixed American	0.00667%	15,002
Remaining individualsnot grpmax-eligible	0.0032%	31,229
African / African-American	0.00133%	74,924

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.Asp528=
Coding: c.1584T>C
MANE Select: NM_002863
Type: single nucleotide variant
Location: chr14:50913065 (GRCh38)
Gene constraint: LOEUF 1.048 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 92.87 · 19 PDB

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 p.Asp528Asn Uncertain significance ★★ ⚠ same residue
PYGL c.1404-1G>A Pathogenic/Likely pathogenic ★★ same condition
PYGL c.1620+1G>A Pathogenic/Likely pathogenic ★★ same condition
PYGL c.1620+1G>C Pathogenic ★★ same condition
PYGL c.1768+1G>A Pathogenic ★★ same condition
PYGL c.772+1G>A Pathogenic/Likely pathogenic ★★ same condition
PYGL p.Arg576Ter Pathogenic ★★ same condition
PYGL p.Arg94Ter 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-asp528 (accessed [today's date]).

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