Is PYGM p.Phe710del (c.2125TTC[1]) pathogenic?

PYGM p.Phe710del (c.2125TTC[1]) is classified Pathogenic/Likely pathogenic in PYGM (ClinVar, Multiple submitters, 9 submitters; last evaluated 2024-06-15). Ultra-rare (popmax 0.0668%, eas); Associated with glycogen storage disease V.

What condition is associated with PYGM p.Phe710del (c.2125TTC[1])?

PYGM p.Phe710del (c.2125TTC[1]) is associated with glycogen storage disease V (ClinVar).

How common is PYGM p.Phe710del (c.2125TTC[1]) in the general population?

PYGM p.Phe710del (c.2125TTC[1]) is ultra-rare (popmax 0.0668%, eas) (gnomAD).

PYGM p.Phe710del

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.2125TTC[1] · rs527236147 · VCV139609

Pathogenic/Likely pathogenic Multiple submitters

Classification

Pathogenic/Likely pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 9 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0668%, eas)

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 · substitutions only
Constraint at this position
Conservation	phyloP 7.9	GERP 1.6, phastCons 1

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0668% East Asian · 30/44,882 alleles

Filtering AF 0.0481% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0417%

Overall 0.00212% 31/1,461,888 alleles · ultra-rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.0668%	1,496
European (non-Finnish)	8.47e-05%	1,180,018

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.Phe710del
Coding: c.2125TTC[1]
MANE Select: NM_005609
dbSNP: rs527236147
Type: Microsatellite
Location: chr11:64750423 (GRCh38)
Gene constraint: LOEUF 0.962 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 94.41 · 1 PDB
Residue 710: a β-strand; 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.Gln220fs Pathogenic/Likely pathogenic ★★ same condition
PYGM p.Lys170del Pathogenic/Likely pathogenic ★★ same condition
PYGM c.772+2_772+3del Pathogenic ★ same condition
PYGM p.Leu579del Likely pathogenic ★ same condition
PYGM p.Tyr53del Likely pathogenic ★ same condition
PYGM p.Glu434del Uncertain significance ★ same condition
PYGM c.345+2TG[3] Likely benign ★ same condition
PYGM c.528+4AGC[3] Likely benign ★ 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-phe710del (accessed [today's date]).

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