Is PYGL p.Tyr727= (c.2181C>T) pathogenic?

PYGL p.Tyr727= (c.2181C>T) is classified Likely benign in PYGL (ClinVar, Single submitter, 1 submitter; last evaluated 2022-10-28). Very rare (popmax 0.00234%, sas); Associated with glycogen storage disease VI.

What condition is associated with PYGL p.Tyr727= (c.2181C>T)?

PYGL p.Tyr727= (c.2181C>T) is associated with glycogen storage disease VI (ClinVar).

How common is PYGL p.Tyr727= (c.2181C>T) in the general population?

PYGL p.Tyr727= (c.2181C>T) is very rare (popmax 0.00234%, sas) (gnomAD).

PYGL p.Tyr727=

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.2181C>T · rs756773559 · VCV2720734

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00234%, sas)

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	all four deltas below 0.2 · G>C here scores Δ0.38 · evaluated, not missing
Constraint at this position
Conservation	phyloP -1.5	GERP -3.9
Overall
CADD	0.533	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00234% South Asian · 2/85,622 alleles

Filtering AF 0.00109% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000891%

Overall 0.00151% 20/1,325,560 alleles · very rare exomes 17/1,181,804 · genomes 3/143,756 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.00234%	42,811
Remaining individualsnot grpmax-eligible	0.002%	50,124
European (non-Finnish)	0.00179%	55,863

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.Tyr727=
Coding: c.2181C>T
MANE Select: NM_002863
dbSNP: rs756773559
Type: single nucleotide variant
Location: chr14:50908952 (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.Tyr727Ter Likely pathogenic ★ same residue
PYGL p.Tyr727Ser 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

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-tyr727 (accessed [today's date]).

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