Is PYGM p.Pro348= (c.1044C>T) pathogenic?

PYGM p.Pro348= (c.1044C>T) is classified Likely benign in PYGM (ClinVar, Single submitter, 1 submitter; last evaluated 2025-04-14). Very rare (popmax 0.00891%, eas); Associated with glycogen storage disease V.

What condition is associated with PYGM p.Pro348= (c.1044C>T)?

PYGM p.Pro348= (c.1044C>T) is associated with glycogen storage disease V (ClinVar).

How common is PYGM p.Pro348= (c.1044C>T) in the general population?

PYGM p.Pro348= (c.1044C>T) is very rare (popmax 0.00891%, eas) (gnomAD).

PYGM p.Pro348=

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.1044C>T · rs763750599 · VCV1086125

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00891%, 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	<0.2	all four deltas below 0.2 · G>T here scores Δ0.23 · evaluated, not missing
Constraint at this position
Conservation	phyloP -6.2	GERP -3.9
Overall
CADD	2.077	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00891% East Asian · 4/44,892 alleles

Filtering AF 0.00298% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0018%

Overall 0.000868% 14/1,613,712 alleles · very rare exomes 13/1,461,564 · genomes 1/152,148 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00891%	11,223
African / African-American	0.00267%	37,448
Remaining individualsnot grpmax-eligible	0.0016%	62,480
South Asian	0.0011%	91,086
European (non-Finnish)	0.000508%	196,660

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.Pro348=
Coding: c.1044C>T
MANE Select: NM_005609
dbSNP: rs763750599
Type: single nucleotide variant
Location: chr11:64754301 (GRCh38)
Gene constraint: LOEUF 0.962 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 94.41 · 1 PDB
Residue 348: 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

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.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
PYGM c.1768+2T>G Pathogenic/Likely pathogenic ★★ same condition
PYGM c.1827+1G>C 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-pro348 (accessed [today's date]).

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