Is PYGM p.Asp718fs (c.2154del) pathogenic?

PYGM p.Asp718fs (c.2154del) is classified Pathogenic in PYGM (ClinVar, Single submitter, 1 submitter; last evaluated 2021-04-06). No gnomAD frequency available for this variant; Associated with glycogen storage disease V.

What condition is associated with PYGM p.Asp718fs (c.2154del)?

PYGM p.Asp718fs (c.2154del) is associated with glycogen storage disease V (ClinVar).

How common is PYGM p.Asp718fs (c.2154del) in the general population?

PYGM p.Asp718fs (c.2154del) is no gnomAD frequency available for this variant (gnomAD).

PYGM p.Asp718fs

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.2154del · rs2135828360 · VCV1351367

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Not reported

no gnomAD frequency available for this variant

Conditions

glycogen storage disease V

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function
NMD	predicted	premature termination codon in exon 17 of 20
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 7.7	GERP 1.6, phastCons 1

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

dbSNP / gnomAD

No gnomAD frequency available for this variant. This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: PYGM
Protein: p.Asp718fs
Coding: c.2154del
MANE Select: NM_005609
dbSNP: rs2135828360
Type: Deletion
Location: chr11:64750399 (GRCh38)
Gene constraint: LOEUF 0.962 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 94.41 · 1 PDB
Residue 718: 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 c.2177_2177+3del Likely pathogenic ★★ same condition
PYGM p.Ala55fs Pathogenic ★★ same condition
PYGM p.Arg161_Tyr162insTer Pathogenic/Likely pathogenic ★★ same condition
PYGM p.Arg194fs Pathogenic/Likely pathogenic ★★ same condition
PYGM p.Asn454_Leu464del Pathogenic/Likely pathogenic ★★ same condition
PYGM p.Glu125fs Pathogenic ★★ same condition
PYGM p.Glu27fs Pathogenic ★★ same condition
PYGM p.Glu797fs 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-asp718fs (accessed [today's date]).

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