Is PYGM p.Arg715= (c.2143C>A) pathogenic?

PYGM p.Arg715= (c.2143C>A) is classified Likely benign in PYGM (ClinVar, Single submitter, 2 submitters; last evaluated 2020-06-16). Very rare (popmax 0.00267%, afr); Associated with glycogen storage disease V.

What condition is associated with PYGM p.Arg715= (c.2143C>A)?

PYGM p.Arg715= (c.2143C>A) is associated with glycogen storage disease V (ClinVar).

How common is PYGM p.Arg715= (c.2143C>A) in the general population?

PYGM p.Arg715= (c.2143C>A) is very rare (popmax 0.00267%, afr) (gnomAD).

PYGM p.Arg715=

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.2143C>A · rs780656375 · VCV992136

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

very rare (popmax 0.00267%, 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	all four deltas below 0.2 · G>A here scores Δ0.95 · evaluated, not missing
Constraint at this position
Conservation	phyloP 1.4	GERP 0.57, phastCons 1
Overall
CADD	8.637	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00267% African / African-American · 2/74,978 alleles

Filtering AF 0.000443% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000166%

Overall 0.000186% 3/1,613,972 alleles · very rare exomes 3/1,461,850 · genomes 0/152,122 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00267%	37,489
European (non-Finnish)	8.47e-05%	1,179,990

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.Arg715=
Coding: c.2143C>A
MANE Select: NM_005609
dbSNP: rs780656375
Type: single nucleotide variant
Location: chr11:64750410 (GRCh38)
Gene constraint: LOEUF 0.962 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 94.41 · 1 PDB
Residue 715: 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.Arg715Trp Conflicting classifications of pathogenicity ★ ⚠ same residue
PYGM p.Arg715Gln 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

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-arg715 (accessed [today's date]).

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