Is PYGL p.Thr49= (c.147C>T) pathogenic?

PYGL p.Thr49= (c.147C>T) is classified Conflicting classifications of pathogenicity in PYGL (ClinVar, Conflicting submitters, 4 submitters; last evaluated 2025-11-09). Ultra-rare (popmax 0.0864%, nfe); Associated with glycogen storage disease VI.

What condition is associated with PYGL p.Thr49= (c.147C>T)?

PYGL p.Thr49= (c.147C>T) is associated with glycogen storage disease VI (ClinVar).

How common is PYGL p.Thr49= (c.147C>T) in the general population?

PYGL p.Thr49= (c.147C>T) is ultra-rare (popmax 0.0864%, nfe) (gnomAD).

PYGL p.Thr49=

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.147C>T · rs139338050 · VCV711568

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 4 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0864%, nfe)

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 -0.6	GERP -3.5, phastCons 0.003
Overall
CADD	10.42	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0864% European (non-Finnish) · 1,020/1,179,916 alleles

Filtering AF 0.082% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0802%

Overall 0.0667% 1,076/1,613,872 alleles · ultra-rare exomes 1,007/1,461,508 · genomes 69/152,364 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.0864%	1,157
Remaining individualsnot grpmax-eligible	0.048%	2,083
Admixed American	0.02%	5,003
Middle Eastern	0.0165%	6,062
African / African-American	0.012%	8,340
Finnishnot grpmax-eligible	0.00313%	31,927
South Asian	0.0022%	45,542

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.Thr49=
Coding: c.147C>T
MANE Select: NM_002863
dbSNP: rs139338050
Type: single nucleotide variant
Location: chr14:50944257 (GRCh38)
Gene constraint: LOEUF 1.048 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 92.87 · 19 PDB
Residue 49: 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-thr49 (accessed [today's date]).

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