Is PYGM p.Glu703= (c.2109G>A) pathogenic?

PYGM p.Glu703= (c.2109G>A) is classified Benign/Likely benign in PYGM (ClinVar, Multiple submitters, 5 submitters; last evaluated 2026-01-21). Rare (popmax 0.586%, amr); Associated with glycogen storage disease V.

What condition is associated with PYGM p.Glu703= (c.2109G>A)?

PYGM p.Glu703= (c.2109G>A) is associated with glycogen storage disease V (ClinVar).

How common is PYGM p.Glu703= (c.2109G>A) in the general population?

PYGM p.Glu703= (c.2109G>A) is rare (popmax 0.586%, amr) (gnomAD).

PYGM p.Glu703=

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.2109G>A · rs200537357 · VCV513919

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 5 submitters

gnomAD v4.1

Rare

rare (popmax 0.586%, amr)

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 1.8	GERP -0.56, phastCons 1
Overall
CADD	11.63	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.586% Admixed American · 352/60,018 alleles

Filtering AF 0.536% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.516%

Overall 0.0229% 369/1,614,140 alleles · rare exomes 196/1,461,890 · genomes 173/152,250 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.586%	171
Remaining individualsnot grpmax-eligible	0.0144%	6,945
African / African-American	0.004%	25,012
European (non-Finnish)	0.000424%	235,996

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.Glu703=
Coding: c.2109G>A
MANE Select: NM_005609
dbSNP: rs200537357
Type: single nucleotide variant
Location: chr11:64750444 (GRCh38)
Gene constraint: LOEUF 0.962 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 94.41 · 1 PDB
Residue 703: an α-helix; a UniProt-annotated variant site (in gsd5)

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.Glu703Lys 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-glu703 (accessed [today's date]).

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