Is PYGL p.Thr672= (c.2016C>T) pathogenic?

PYGL p.Thr672= (c.2016C>T) is classified Benign in PYGL (ClinVar, Multiple submitters, 7 submitters; last evaluated 2026-02-01). Common (popmax 41.1%, afr) — too common for a highly-penetrant pathogenic allele; Associated with glycogen storage disease VI.

What condition is associated with PYGL p.Thr672= (c.2016C>T)?

PYGL p.Thr672= (c.2016C>T) is associated with glycogen storage disease VI (ClinVar).

PYGL p.Thr672=

Q: How common is PYGL p.Thr672= (c.2016C>T) in the general population?

PYGL p.Thr672= (c.2016C>T) is common (popmax 41.1%, afr) — 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.2016C>T · rs15669 · VCV258836

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 7 submitters

gnomAD v4.1

Common

common (popmax 41.1%, afr) — 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	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP -20	GERP -3.6
Overall
CADD	0.008	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 41.1% African / African-American · 30,768/74,936 alleles

Filtering AF 40.7% ClinGen BA1/BS1 input FAF95, joint · FAF99 40.5%

Overall 14.1% 227,129/1,613,832 alleles · common exomes 195,900/1,461,712 · genomes 31,229/152,120 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	41.1%	2
South Asian	18.8%	5
Middle Eastern	15.7%	6
East Asian	14.3%	7
Remaining individualsnot grpmax-eligible	14.3%	7
Ashkenazi Jewishnot grpmax-eligible	13.6%	7
Finnishnot grpmax-eligible	12.8%	8
Amishnot grpmax-eligible	12.3%	8
European (non-Finnish)	12.2%	8
Admixed American	10.4%	10

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.Thr672=
Coding: c.2016C>T
MANE Select: NM_002863
dbSNP: rs15669
Type: single nucleotide variant
Location: chr14:50910056 (GRCh38)
Gene constraint: LOEUF 1.048 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 92.87 · 19 PDB
Residue 672: a turn

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.Thr672Pro 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
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-thr672 (accessed [today's date]).

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