Is PYGL p.Arg172Ter (c.514C>T) pathogenic?

PYGL p.Arg172Ter (c.514C>T) is classified Pathogenic in PYGL (ClinVar, Single submitter, 1 submitter; last evaluated 2022-05-15). Very rare (popmax 0.00329%, sas); Associated with glycogen storage disease VI.

What condition is associated with PYGL p.Arg172Ter (c.514C>T)?

PYGL p.Arg172Ter (c.514C>T) is associated with glycogen storage disease VI (ClinVar).

How common is PYGL p.Arg172Ter (c.514C>T) in the general population?

PYGL p.Arg172Ter (c.514C>T) is very rare (popmax 0.00329%, sas) (gnomAD).

PYGL p.Arg172Ter

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.514C>T · rs2050602182 · VCV1988522

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

nonsense (stop-gain)

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.00329%, sas)

Conditions

glycogen storage disease VI

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	nonsense (stop-gain)	predicted loss-of-function
NMD	predicted	premature termination codon in exon 4 of 20
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 4.4	GERP -1.4, phastCons 1
Overall
CADD	40.0	PHRED · no single calibrated threshold — expert panels disagree

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00329% South Asian · 3/91,050 alleles

Filtering AF 0.000875% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000443%

Overall 0.00031% 5/1,613,420 alleles · very rare exomes 5/1,461,342 · genomes 0/152,078 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.00329%	30,350
Remaining individualsnot grpmax-eligible	0.0016%	62,474
European (non-Finnish)	8.48e-05%	1,179,567

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.Arg172Ter
Coding: c.514C>T
MANE Select: NM_002863
dbSNP: rs2050602182
Type: single nucleotide variant
Location: chr14:50931687 (GRCh38)
Gene constraint: LOEUF 1.048 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 92.87 · 19 PDB
Residue 172: 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-arg172ter (accessed [today's date]).

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