Is PYGM p.Val370= (c.1110G>A) pathogenic?

PYGM p.Val370= (c.1110G>A) is classified Conflicting classifications of pathogenicity in PYGM (ClinVar, Conflicting submitters, 4 submitters; last evaluated 2024-05-06). Ultra-rare (popmax 0.027%, eas); Associated with glycogen storage disease V.

What condition is associated with PYGM p.Val370= (c.1110G>A)?

PYGM p.Val370= (c.1110G>A) is associated with glycogen storage disease V (ClinVar).

How common is PYGM p.Val370= (c.1110G>A) in the general population?

PYGM p.Val370= (c.1110G>A) is ultra-rare (popmax 0.027%, eas) (gnomAD).

PYGM p.Val370=

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.1110G>A · rs372719040 · VCV719046

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 4 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.027%, 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 · no allele here is in the release
Constraint at this position
Conservation	phyloP 1.3	GERP 0.8, phastCons 1
Overall
CADD	9.482	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.027% East Asian · 12/44,494 alleles

Filtering AF 0.0155% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0122%

Overall 0.00187% 30/1,604,704 alleles · ultra-rare exomes 30/1,452,642 · genomes 0/152,062 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.027%	3,708
Remaining individualsnot grpmax-eligible	0.0177%	5,651
South Asian	0.00335%	29,869
Admixed American	0.0017%	58,772
European (non-Finnish)	0.000255%	391,856

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.Val370=
Coding: c.1110G>A
MANE Select: NM_005609
dbSNP: rs372719040
Type: single nucleotide variant
Location: chr11:64754008 (GRCh38)
Gene constraint: LOEUF 0.962 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 94.41 · 1 PDB
Residue 370: 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-val370 (accessed [today's date]).

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