Is GYS2 p.Asp93= (c.279C>T) pathogenic?

GYS2 p.Asp93= (c.279C>T) is classified Conflicting classifications of pathogenicity in GYS2 (ClinVar, Conflicting submitters, 2 submitters; last evaluated 2024-02-26). Ultra-rare (popmax 0.0164%, mid); Associated with glycogen storage disorder due to hepatic glycogen synthase deficiency.

What condition is associated with GYS2 p.Asp93= (c.279C>T)?

GYS2 p.Asp93= (c.279C>T) is associated with glycogen storage disorder due to hepatic glycogen synthase deficiency (ClinVar).

How common is GYS2 p.Asp93= (c.279C>T) in the general population?

GYS2 p.Asp93= (c.279C>T) is ultra-rare (popmax 0.0164%, mid) (gnomAD).

GYS2 p.Asp93=

Q: How is Glycogen storage disease due to hepatic glycogen synthase deficiency inherited?

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

c.279C>T · rs779704436 · VCV308010

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0164%, mid)

Conditions

glycogen storage disorder due to hepatic glycogen synthase deficiency

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 -11	GERP -3.8
Overall
CADD	5.422	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0164% Middle Eastern · 1/6,084 alleles

Filtering AF 0.00428% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00295%

Overall 0.00155% 25/1,613,440 alleles · ultra-rare exomes 23/1,461,354 · genomes 2/152,086 · joint denominator

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0164%	6,084
Admixed American	0.01%	9,997
East Asian	0.00669%	14,957
South Asian	0.00549%	18,214
Remaining individualsnot grpmax-eligible	0.0016%	62,470
African / African-American	0.00134%	74,878
European (non-Finnish)	0.000678%	147,462

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: GYS2
Protein: p.Asp93=
Coding: c.279C>T
MANE Select: NM_021957
dbSNP: rs779704436
Type: single nucleotide variant
Location: chr12:21580366 (GRCh38)
Gene constraint: LOEUF 1.277 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 87.08

Full GYS2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

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

For Glycogen storage disease due to hepatic glycogen synthase deficiency (Orphanet):

Inheritance: Autosomal recessive
Onset: Childhood

Similar variants

GYS2 p.Asp93Glu Likely benign ★ same residue
GYS2 c.1062+1G>T Pathogenic/Likely pathogenic ★★ same condition
GYS2 c.1230-1G>A Likely pathogenic ★★ same condition
GYS2 c.495+1G>T Pathogenic/Likely pathogenic ★★ same condition
GYS2 p.Ala339Pro Pathogenic/Likely pathogenic ★★ same condition
GYS2 p.Arg147Ter Likely pathogenic ★★ same condition
GYS2 p.Arg192Ter Pathogenic/Likely pathogenic ★★ same condition
GYS2 p.Arg246Ter 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/gys2-p-asp93 (accessed [today's date]).

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