Is PYGL p.Asp340= (c.1020C>T) pathogenic?

PYGL p.Asp340= (c.1020C>T) is classified Benign in PYGL (ClinVar, Multiple submitters, 7 submitters; last evaluated 2026-02-04). Common (popmax 42.6%, eas) — too common for a highly-penetrant pathogenic allele; Associated with glycogen storage disease VI.

What condition is associated with PYGL p.Asp340= (c.1020C>T)?

PYGL p.Asp340= (c.1020C>T) is associated with glycogen storage disease VI (ClinVar).

PYGL p.Asp340=

Q: How common is PYGL p.Asp340= (c.1020C>T) in the general population?

PYGL p.Asp340= (c.1020C>T) is common (popmax 42.6%, eas) — too common for a highly-penetrant pathogenic allele (gnomAD).

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.1020C>T · rs2075643 · VCV258830

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 7 submitters

gnomAD v4.1

Common

common (popmax 42.6%, eas) — too common for a highly-penetrant pathogenic allele

Conditions

glycogen storage disease VI

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 2.1	GERP 1.9, phastCons 1
Overall
CADD	9.614	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 42.6% East Asian · 19,097/44,866 alleles

Filtering AF 42.1% ClinGen BA1/BS1 input FAF95, joint · FAF99 41.9%

Overall 19.2% 310,468/1,612,936 alleles · common exomes 284,209/1,460,720 · genomes 26,259/152,216 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	42.6%	2
Admixed American	42.2%	2
Middle Eastern	26.6%	4
South Asian	22.1%	5
Remaining individualsnot grpmax-eligible	20.4%	5
Finnishnot grpmax-eligible	19.8%	5
European (non-Finnish)	17.7%	6
Ashkenazi Jewishnot grpmax-eligible	16.6%	6
Amishnot grpmax-eligible	8.44%	12
African / African-American	6.43%	16

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.Asp340=
Coding: c.1020C>T
MANE Select: NM_002863
dbSNP: rs2075643
Type: single nucleotide variant
Location: chr14:50916714 (GRCh38)
Gene constraint: LOEUF 1.048 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 92.87 · 19 PDB
Residue 340: 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.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
PYGL p.Gln577Ter 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/pygl-p-asp340 (accessed [today's date]).

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