Is PYGM p.Ser172= (c.516C>T) pathogenic?

PYGM p.Ser172= (c.516C>T) is classified Likely benign in PYGM (ClinVar, Multiple submitters, 5 submitters; last evaluated 2026-01-16). Rare (popmax 0.253%, afr); Associated with glycogen storage disease V.

What condition is associated with PYGM p.Ser172= (c.516C>T)?

PYGM p.Ser172= (c.516C>T) is associated with glycogen storage disease V (ClinVar).

How common is PYGM p.Ser172= (c.516C>T) in the general population?

PYGM p.Ser172= (c.516C>T) is rare (popmax 0.253%, afr) (gnomAD).

PYGM p.Ser172=

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.516C>T · rs147402432 · VCV259837

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 5 submitters

gnomAD v4.1

Rare

rare (popmax 0.253%, afr)

Conditions

glycogen storage disease V

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 -3.4	GERP -3.9
Overall
CADD	7.717	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.253% African / African-American · 190/75,022 alleles

Filtering AF 0.224% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.212%

Overall 0.0148% 238/1,613,000 alleles · rare exomes 124/1,460,750 · genomes 114/152,250 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.253%	395
Admixed American	0.0117%	8,574
South Asian	0.00988%	10,119
Remaining individualsnot grpmax-eligible	0.0096%	10,413
European (non-Finnish)	0.00221%	45,345

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.Ser172=
Coding: c.516C>T
MANE Select: NM_005609
dbSNP: rs147402432
Type: single nucleotide variant
Location: chr11:64758258 (GRCh38)
Gene constraint: LOEUF 0.962 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 94.41 · 1 PDB
Residue 172: a UniProt-annotated variant site (in gsd5); a β-strand

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-ser172 (accessed [today's date]).

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