Is PYGL p.Ser31= (c.93T>C) pathogenic?

PYGL p.Ser31= (c.93T>C) is classified Benign in PYGL (ClinVar, Multiple submitters, 8 submitters; last evaluated 2026-01-31). Common (popmax 12.3%, eas) — too common for a highly-penetrant pathogenic allele; Associated with glycogen storage disease VI.

What condition is associated with PYGL p.Ser31= (c.93T>C)?

PYGL p.Ser31= (c.93T>C) is associated with glycogen storage disease VI (ClinVar).

PYGL p.Ser31=

Q: How common is PYGL p.Ser31= (c.93T>C) in the general population?

PYGL p.Ser31= (c.93T>C) is common (popmax 12.3%, 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.93T>C · rs17123244 · VCV258849

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 8 submitters

gnomAD v4.1

Common

common (popmax 12.3%, 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 1.7	GERP 0.85, phastCons 1
Overall
CADD	12.99	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 12.3% East Asian · 5,533/44,820 alleles

Filtering AF 12.1% ClinGen BA1/BS1 input FAF95, joint · FAF99 12%

Overall 4.62% 74,545/1,612,674 alleles · common exomes 67,348/1,461,614 · genomes 7,197/151,060 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	12.3%	8
Admixed American	8.88%	11
South Asian	7.59%	13
Remaining individualsnot grpmax-eligible	4.84%	21
African / African-American	4.62%	22
European (non-Finnish)	4.05%	25
Middle Eastern	4.01%	25
Finnishnot grpmax-eligible	2.76%	36
Ashkenazi Jewishnot grpmax-eligible	1.95%	51
Amishnot grpmax-eligible	0.881%	114

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.Ser31=
Coding: c.93T>C
MANE Select: NM_002863
dbSNP: rs17123244
Type: single nucleotide variant
Location: chr14:50944311 (GRCh38)
Gene constraint: LOEUF 1.048 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 92.87 · 19 PDB
Residue 31: an α-helix

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-ser31 (accessed [today's date]).

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