Is PYGM p.Arg50Ter (c.148C>T) pathogenic?

PYGM p.Arg50Ter (c.148C>T) is classified Pathogenic/Likely pathogenic in PYGM (ClinVar, Multiple submitters, 42 submitters; last evaluated 2026-02-22). Rare (popmax 0.363%, nfe); Associated with Skeletal muscle channelopathy.

What condition is associated with PYGM p.Arg50Ter (c.148C>T)?

PYGM p.Arg50Ter (c.148C>T) is associated with Skeletal muscle channelopathy, disorder of glycogen metabolism, retinal disorder (ClinVar).

How common is PYGM p.Arg50Ter (c.148C>T) in the general population?

PYGM p.Arg50Ter (c.148C>T) is rare (popmax 0.363%, nfe) (gnomAD).

PYGM p.Arg50Ter

c.148C>T · rs116987552 · VCV2298

Pathogenic/Likely pathogenic Multiple submitters

Classification

Pathogenic/Likely pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 42 submitters

Consequence

nonsense (stop-gain)

predicted LoF

gnomAD v4.1

Rare

rare (popmax 0.363%, nfe)

Conditions

Skeletal muscle channelopathy

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	nonsense (stop-gain)	predicted loss-of-function
NMD	predicted	premature termination codon in exon 1 of 20
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.89	GERP -0.38, phastCons 0.18
Overall
CADD	36.0	PHRED · no single calibrated threshold — expert panels disagree

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.363% European (non-Finnish) · 4,285/1,180,038 alleles

Filtering AF 0.354% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.35%

Overall 0.284% 4,580/1,614,240 alleles · rare exomes 4,312/1,461,882 · genomes 268/152,358 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.363%	275
Remaining individualsnot grpmax-eligible	0.221%	453
Admixed American	0.127%	790
African / African-American	0.0559%	1,788
Finnishnot grpmax-eligible	0.0547%	1,830
Ashkenazi Jewishnot grpmax-eligible	0.00676%	14,803
East Asian	0.00223%	44,882
South Asian	0.0011%	91,084

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.Arg50Ter
Coding: c.148C>T
MANE Select: NM_005609
dbSNP: rs116987552
Type: single nucleotide variant
Location: chr11:64759751 (GRCh38)
Gene constraint: LOEUF 0.962 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 94.41 · 1 PDB
Residue 50: a UniProt-annotated variant site (in gsd5); an α-helix

Full PYGM gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Skeletal muscle channelopathy

Also linked: disorder of glycogen metabolism retinal disorder glycogen storage disease V hereditary skeletal muscle disorder

Similar variants

PYGM p.Arg50Gln Uncertain significance ★★ same residue
PYGM p.Arg50= Likely benign ★ 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-arg50ter (accessed [today's date]).

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