GYS1 p.Phe342=

Q: Is GYS1 p.Phe342= (c.1026C>T) pathogenic?

GYS1 p.Phe342= (c.1026C>T) is classified Benign in GYS1 (ClinVar, Multiple submitters, 8 submitters; last evaluated 2026-02-04). Common (popmax 36.7%, mid) — too common for a highly-penetrant pathogenic allele; Associated with glycogen storage disease due to muscle and heart glycogen synthase deficiency.

Q: What condition is associated with GYS1 p.Phe342= (c.1026C>T)?

GYS1 p.Phe342= (c.1026C>T) is associated with glycogen storage disease due to muscle and heart glycogen synthase deficiency (ClinVar).

Q: How common is GYS1 p.Phe342= (c.1026C>T) in the general population?

GYS1 p.Phe342= (c.1026C>T) is common (popmax 36.7%, mid) — too common for a highly-penetrant pathogenic allele (gnomAD).

Q: How is Glycogen storage disease due to muscle and heart glycogen synthase deficiency inherited?

Typically Autosomal recessive (Orphanet). A genetic counselor can assess individual risk for a family.

c.1026C>T · rs5464 · VCV329818

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 8 submitters

gnomAD v4.1

Common

common (popmax 36.7%, mid) — too common for a highly-penetrant pathogenic allele

Conditions

glycogen storage disease due to muscle and heart glycogen synthase deficiency

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.019	moderately benign-leaning
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 3.9	phastCons 1
Overall
CADD	10.6	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 36.7% Middle Eastern · 2,224/6,058 alleles

Filtering AF 35.4% ClinGen BA1/BS1 input FAF95, joint · FAF99 34.9%

Overall 28.4% 457,475/1,612,778 alleles · common exomes 414,568/1,460,916 · genomes 42,907/151,862 · joint denominator

Ancestry group	Frequency	1 in
Middle Easterngrpmax	36.7%	3
European (non-Finnish)	29.4%	3
Ashkenazi Jewishnot grpmax-eligible	29.4%	3
African / African-American	29.3%	3
Remaining individualsnot grpmax-eligible	27.7%	4
Finnishnot grpmax-eligible	26.7%	4
Admixed American	25%	4
Amishnot grpmax-eligible	24.7%	4
East Asian	21.9%	5
South Asian	20.2%	5

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: GYS1
Protein: p.Phe342=
Coding: c.1026C>T
MANE Select: NM_002103
dbSNP: rs5464
Type: single nucleotide variant
Location: chr19:48982291 (GRCh38)
Gene constraint: LOEUF 0.898 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 84.83 · 9 PDB
Residue 342: an α-helix

Full GYS1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

glycogen storage disease due to muscle and heart glycogen synthase deficiency — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Glycogen storage disease due to muscle and heart glycogen synthase deficiency (Orphanet):

Inheritance: Autosomal recessive
Onset: Childhood

Similar variants

GYS1 c.1645+1G>A Likely pathogenic ★★ same condition
GYS1 c.678+1G>A Pathogenic/Likely pathogenic ★★ same condition
GYS1 p.Arg462Ter Pathogenic ★★ same condition
GYS1 p.Glu539Ter Pathogenic/Likely pathogenic ★★ same condition
GYS1 p.Ala167Glu Uncertain significance ★★ ⚠ same condition
GYS1 p.Ala193Val Uncertain significance ★★ ⚠ same condition
GYS1 p.Ala252Thr Uncertain significance ★★ ⚠ same condition
GYS1 p.Ala27Val Uncertain significance ★★ ⚠ 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/gys1-p-phe342 (accessed [today's date]).

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