Is PYGL p.Arg576Ter (c.1726C>T) pathogenic?

PYGL p.Arg576Ter (c.1726C>T) is classified Pathogenic in PYGL (ClinVar, Multiple submitters, 2 submitters; last evaluated 2023-05-03). Very rare (popmax 0.00446%, eas); Associated with PYGL-related disorder.

What condition is associated with PYGL p.Arg576Ter (c.1726C>T)?

PYGL p.Arg576Ter (c.1726C>T) is associated with PYGL-related disorder, glycogen storage disease VI (ClinVar).

How common is PYGL p.Arg576Ter (c.1726C>T) in the general population?

PYGL p.Arg576Ter (c.1726C>T) is very rare (popmax 0.00446%, eas) (gnomAD).

PYGL p.Arg576Ter

c.1726C>T · rs774646420 · VCV1076414

Pathogenic Multiple submitters

Classification

Pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

Consequence

nonsense (stop-gain)

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.00446%, eas)

Conditions

PYGL-related disorder

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 14 of 20
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 5	GERP 1, phastCons 1
Overall
CADD	41.0	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 0.00446% East Asian · 2/44,886 alleles

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

Overall 0.00118% 19/1,614,028 alleles · very rare exomes 18/1,461,872 · genomes 1/152,156 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00446%	22,443
South Asian	0.00329%	30,365
Finnishnot grpmax-eligible	0.00156%	64,032
African / African-American	0.00134%	74,904
European (non-Finnish)	0.00102%	98,335

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.Arg576Ter
Coding: c.1726C>T
MANE Select: NM_002863
dbSNP: rs774646420
Type: single nucleotide variant
Location: chr14:50912198 (GRCh38)
Gene constraint: LOEUF 1.048 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 92.87 · 19 PDB
Residue 576: a turn

Full PYGL gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

PYGL-related disorder

Also linked: glycogen storage disease VI

Similar variants

PYGL p.Arg576= Likely benign ★★ same residue
PYGL p.Arg576Gln 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.Arg94Ter 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-arg576ter (accessed [today's date]).

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