Is PYGM p.Ile308= (c.924C>T) pathogenic?

PYGM p.Ile308= (c.924C>T) is classified Conflicting classifications of pathogenicity in PYGM (ClinVar, Conflicting submitters, 10 submitters; last evaluated 2026-01-28). Rare (popmax 0.262%, nfe); Associated with glycogen storage disease V.

What condition is associated with PYGM p.Ile308= (c.924C>T)?

PYGM p.Ile308= (c.924C>T) is associated with glycogen storage disease V (ClinVar).

How common is PYGM p.Ile308= (c.924C>T) in the general population?

PYGM p.Ile308= (c.924C>T) is rare (popmax 0.262%, nfe) (gnomAD).

PYGM p.Ile308=

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.924C>T · rs139726186 · VCV198831

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 10 submitters

gnomAD v4.1

Rare

rare (popmax 0.262%, nfe)

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 3.4	GERP -0.25, phastCons 1
Overall
CADD	11.26	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.262% European (non-Finnish) · 3,090/1,180,002 alleles

Filtering AF 0.254% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.251%

Overall 0.22% 3,548/1,613,948 alleles · rare exomes 3,287/1,461,622 · genomes 261/152,326 · joint denominator

Ancestry group	Frequency	1 in
Amishnot grpmax-eligible	1.32%	76
Remaining individualsnot grpmax-eligible	0.296%	338
European (non-Finnish)grpmax	0.262%	382
Admixed American	0.24%	417
Middle Eastern	0.216%	463
Ashkenazi Jewishnot grpmax-eligible	0.176%	569
African / African-American	0.0386%	2,588
South Asian	0.022%	4,554
Finnishnot grpmax-eligible	0.0047%	21,297

Amish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Ile308=
Coding: c.924C>T
MANE Select: NM_005609
dbSNP: rs139726186
Type: single nucleotide variant
Location: chr11:64754768 (GRCh38)
Gene constraint: LOEUF 0.962 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 94.41 · 1 PDB
Residue 308: 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.Ile308fs Pathogenic/Likely pathogenic ★★ 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-ile308 (accessed [today's date]).

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