Is PYGM p.Pro498= (c.1494C>T) pathogenic?

PYGM p.Pro498= (c.1494C>T) is classified Benign in PYGM (ClinVar, Multiple submitters, 9 submitters; last evaluated 2026-02-04). Common (popmax 11.5%, afr) — too common for a highly-penetrant pathogenic allele; Associated with glycogen storage disease V.

What condition is associated with PYGM p.Pro498= (c.1494C>T)?

PYGM p.Pro498= (c.1494C>T) is associated with glycogen storage disease V (ClinVar).

PYGM p.Pro498=

Q: How common is PYGM p.Pro498= (c.1494C>T) in the general population?

PYGM p.Pro498= (c.1494C>T) is common (popmax 11.5%, afr) — too common for a highly-penetrant pathogenic allele (gnomAD).

Q: How is Glycogen storage disease due to muscle glycogen phosphorylase deficiency inherited?

Typically Autosomal recessive (Orphanet). A genetic counselor can assess individual risk for a family.

c.1494C>T · rs11231865 · VCV95292

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 9 submitters

gnomAD v4.1

Common

common (popmax 11.5%, afr) — too common for a highly-penetrant pathogenic allele

Conditions

glycogen storage disease V

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 -7.4	GERP -3.9
Overall
CADD	1.992	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 11.5% African / African-American · 8,591/74,992 alleles

Filtering AF 11.3% ClinGen BA1/BS1 input FAF95, joint · FAF99 11.2%

Overall 0.609% 9,827/1,613,600 alleles · common

Ancestry group	Frequency	1 in
African / African-Americangrpmax	11.5%	9
Admixed American	0.773%	129
Remaining individualsnot grpmax-eligible	0.707%	141
Ashkenazi Jewishnot grpmax-eligible	0.334%	299
Middle Eastern	0.264%	379
South Asian	0.0242%	4,140
European (non-Finnish)	0.0164%	6,112

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: PYGM
Protein: p.Pro498=
Coding: c.1494C>T
MANE Select: NM_005609
dbSNP: rs11231865
Type: single nucleotide variant
Location: chr11:64753097 (GRCh38)
Gene constraint: LOEUF 0.962 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 94.41 · 1 PDB
Residue 498: a UniProt-annotated variant site (in gsd5); an α-helix

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

Disease context

glycogen storage disease V — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Glycogen storage disease due to muscle glycogen phosphorylase deficiency (Orphanet):

Inheritance: Autosomal recessive
Onset: Adolescent, Adult, Childhood

Similar variants

PYGM p.Pro498Ser Uncertain significance ★★ ⚠ same residue
PYGM c.1092+1G>A Likely pathogenic ★★ same condition
PYGM c.1092+1G>C Likely pathogenic ★★ same condition
PYGM c.1239+1G>A Pathogenic/Likely pathogenic ★★ same condition
PYGM c.1240-2A>G Likely pathogenic ★★ same condition
PYGM c.1403+1G>A Pathogenic ★★ same condition
PYGM c.1768+1G>A Pathogenic/Likely pathogenic ★★ same condition
PYGM c.1768+2T>G 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/pygm-p-pro498 (accessed [today's date]).

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