Is PYGM p.Phe317= (c.951C>T) pathogenic?

PYGM p.Phe317= (c.951C>T) is classified Likely benign in PYGM (ClinVar, Multiple submitters, 4 submitters; last evaluated 2025-11-23). Ultra-rare (popmax 0.0836%, mid); Associated with glycogen storage disease V.

What condition is associated with PYGM p.Phe317= (c.951C>T)?

PYGM p.Phe317= (c.951C>T) is associated with glycogen storage disease V (ClinVar).

How common is PYGM p.Phe317= (c.951C>T) in the general population?

PYGM p.Phe317= (c.951C>T) is ultra-rare (popmax 0.0836%, mid) (gnomAD).

PYGM p.Phe317=

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.951C>T · rs71581789 · VCV738831

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0836%, mid)

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 -5	GERP -3.9
Overall
CADD	7.359	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0836% Middle Eastern · 5/5,982 alleles

Filtering AF 0.0329% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0214%

Overall 0.00551% 89/1,613,794 alleles · ultra-rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0836%	1,196
African / African-American	0.0213%	4,689
Admixed American	0.0167%	6,001
Remaining individualsnot grpmax-eligible	0.0096%	10,414
South Asian	0.00659%	15,176
European (non-Finnish)	0.00364%	27,441
Finnishnot grpmax-eligible	0.00313%	31,934
East Asian	0.00223%	44,880

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.Phe317=
Coding: c.951C>T
MANE Select: NM_005609
dbSNP: rs71581789
Type: single nucleotide variant
Location: chr11:64754741 (GRCh38)
Gene constraint: LOEUF 0.962 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 94.41 · 1 PDB
Residue 317: a UniProt-annotated variant site (in gsd5); a binding site

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 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
PYGM c.1827+1G>C 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-phe317 (accessed [today's date]).

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