Is PYGL p.Pro232= (c.696C>T) pathogenic?

PYGL p.Pro232= (c.696C>T) is classified Likely benign in PYGL (ClinVar, Multiple submitters, 2 submitters; last evaluated 2024-10-03). Ultra-rare (popmax 0.0275%, nfe); Associated with glycogen storage disease VI.

What condition is associated with PYGL p.Pro232= (c.696C>T)?

PYGL p.Pro232= (c.696C>T) is associated with glycogen storage disease VI (ClinVar).

How common is PYGL p.Pro232= (c.696C>T) in the general population?

PYGL p.Pro232= (c.696C>T) is ultra-rare (popmax 0.0275%, nfe) (gnomAD).

PYGL p.Pro232=

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.696C>T · rs141485241 · VCV1105605

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0275%, 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 -1.2	GERP -3.9
Overall
CADD	1.987	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0275% European (non-Finnish) · 324/1,180,026 alleles

Filtering AF 0.0249% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.024%

Overall 0.0212% 343/1,614,190 alleles · ultra-rare exomes 322/1,461,850 · genomes 21/152,340 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.0275%	3,642
Remaining individualsnot grpmax-eligible	0.0144%	6,945
African / African-American	0.00533%	18,763
Admixed American	0.00333%	30,016
Finnishnot grpmax-eligible	0.00312%	32,020
East Asian	0.00223%	44,884
South Asian	0.0011%	91,074

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.Pro232=
Coding: c.696C>T
MANE Select: NM_002863
dbSNP: rs141485241
Type: single nucleotide variant
Location: chr14:50921032 (GRCh38)
Gene constraint: LOEUF 1.048 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 92.87 · 19 PDB
Residue 232: 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

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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-pro232 (accessed [today's date]).

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