Is PYGM p.Arg3Trp (c.7C>T) pathogenic?

PYGM p.Arg3Trp (c.7C>T) is classified Uncertain significance in PYGM (ClinVar, Multiple submitters, 6 submitters; last evaluated 2024-12-12). AlphaMissense: likely benign (0.2419); Rare (popmax 0.1%, eas); Associated with glycogen storage disease V.

What condition is associated with PYGM p.Arg3Trp (c.7C>T)?

PYGM p.Arg3Trp (c.7C>T) is associated with glycogen storage disease V (ClinVar).

How common is PYGM p.Arg3Trp (c.7C>T) in the general population?

PYGM p.Arg3Trp (c.7C>T) is rare (popmax 0.1%, eas) (gnomAD).

What do computational predictors say about PYGM p.Arg3Trp (c.7C>T)?

AlphaMissense predicts likely benign (score 0.2419) — an in-silico prediction, not a clinical call.

PYGM p.Arg3Trp

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.7C>T · rs199565370 · VCV878451

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 6 submitters

AlphaMissense

likely benign

0.2419 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.1%, eas)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

glycogen storage disease V

Computational evidence

Protein change
AlphaMissense	0.2419	likely benign
REVEL	0.529	indeterminate
SaProt	LLR -10.12	damaging
⇒ SaProt calls this damaging; AlphaMissense does not; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 3.2	GERP -0.9, phastCons 1
Regional constraint	o/e 0.89	unconstrained · MANE · 13 kb · p 0.00017 · regional, not allelic
Overall
CADD	27.5	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.1% East Asian · 45/44,880 alleles

Filtering AF 0.077% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0688%

Overall 0.00644% 104/1,614,014 alleles · rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.1%	997
African / African-American	0.00666%	15,010
European (non-Finnish)	0.00432%	23,137
Remaining individualsnot grpmax-eligible	0.0032%	31,252
South Asian	0.0011%	91,072

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.Arg3Trp
Coding: c.7C>T
MANE Select: NM_005609
dbSNP: rs199565370
Type: single nucleotide variant
Location: chr11:64759892 (GRCh38)
Gene constraint: LOEUF 0.962 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 94.41 · 1 PDB

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.Arg3Gln Uncertain significance ★★ ⚠ same residue
PYGM p.Arg3Gly 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-arg3trp (accessed [today's date]).

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