Is GYS2 p.Val20= (c.60C>T) pathogenic?

GYS2 p.Val20= (c.60C>T) is classified Likely benign in GYS2 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-12-08). Ultra-rare (popmax 0.0424%, eas); Associated with glycogen storage disorder due to hepatic glycogen synthase deficiency.

What condition is associated with GYS2 p.Val20= (c.60C>T)?

GYS2 p.Val20= (c.60C>T) is associated with glycogen storage disorder due to hepatic glycogen synthase deficiency (ClinVar).

How common is GYS2 p.Val20= (c.60C>T) in the general population?

GYS2 p.Val20= (c.60C>T) is ultra-rare (popmax 0.0424%, eas) (gnomAD).

GYS2 p.Val20=

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.60C>T · rs779375076 · VCV1147612

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.0424%, eas)

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 -4.3	GERP -3.6
Overall
CADD	0.334	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0424% East Asian · 19/44,860 alleles

Filtering AF 0.0277% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.023%

Overall 0.0018% 29/1,612,276 alleles · ultra-rare exomes 22/1,460,190 · genomes 7/152,086 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.0424%	2,361
African / African-American	0.00668%	14,967
South Asian	0.0033%	30,344
Admixed American	0.00167%	59,894
Finnishnot grpmax-eligible	0.00156%	64,012

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.Val20=
Coding: c.60C>T
MANE Select: NM_021957
dbSNP: rs779375076
Type: single nucleotide variant
Location: chr12:21604533 (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 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
GYS2 p.Arg386Ter 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-val20 (accessed [today's date]).

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