Is PHKG2 p.Ser96= (c.288C>T) pathogenic?

PHKG2 p.Ser96= (c.288C>T) is classified Conflicting classifications of pathogenicity in PHKG2 (ClinVar, Conflicting submitters, 7 submitters; last evaluated 2026-01-26). Rare (popmax 0.323%, nfe); Associated with glycogen storage disease IXc.

What condition is associated with PHKG2 p.Ser96= (c.288C>T)?

PHKG2 p.Ser96= (c.288C>T) is associated with glycogen storage disease IXc (ClinVar).

How common is PHKG2 p.Ser96= (c.288C>T) in the general population?

PHKG2 p.Ser96= (c.288C>T) is rare (popmax 0.323%, nfe) (gnomAD).

PHKG2 p.Ser96=

Q: How is Glycogen storage disease due to liver phosphorylase kinase deficiency inherited?

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

c.288C>T · rs56029513 · VCV255783

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 7 submitters

gnomAD v4.1

Rare

rare (popmax 0.323%, nfe)

Conditions

glycogen storage disease IXc

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation/SpliceAI carries the signal.
Splicing
SpliceAI	Δ0.22	acceptor loss, 16 bp away · masked 0 · deltas
Constraint at this position
Conservation	phyloP 4.9	GERP -1.8, phastCons 1
Overall
CADD	10.92	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.323% European (non-Finnish) · 3,816/1,179,656 alleles

Filtering AF 0.315% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.311%

Overall 0.247% 3,994/1,613,774 alleles · rare exomes 3,766/1,461,486 · genomes 228/152,288 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.323%	309
Remaining individualsnot grpmax-eligible	0.155%	644
Finnishnot grpmax-eligible	0.0718%	1,392
African / African-American	0.032%	3,126
Admixed American	0.0183%	5,457

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: PHKG2
Protein: p.Ser96=
Coding: c.288C>T
MANE Select: NM_000294
dbSNP: rs56029513
Type: single nucleotide variant
Location: chr16:30751565 (GRCh38)
Gene constraint: LOEUF 0.876 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 83.77 · 1 PDB
Residue 96: the protein kinase domain; a β-strand

Full PHKG2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

glycogen storage disease IXc — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Glycogen storage disease due to liver phosphorylase kinase deficiency (Orphanet):

Inheritance: Autosomal recessive, X-linked recessive
Onset: Childhood
Prevalence: 1-9 / 100 000 (Europe)

Similar variants

PHKG2 c.96-11G>A Pathogenic/Likely pathogenic ★★ same condition
PHKG2 p.Arg152Ter Pathogenic/Likely pathogenic ★★ same condition
PHKG2 p.Arg185Ter Pathogenic ★★ same condition
PHKG2 p.Arg279Cys Pathogenic/Likely pathogenic ★★ same condition
PHKG2 p.Arg309Trp Likely pathogenic ★★ ⚠ same condition
PHKG2 p.Arg44Ter Pathogenic ★★ same condition
PHKG2 p.Arg76Ter Pathogenic/Likely pathogenic ★★ same condition
PHKG2 p.Asp215Asn 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/phkg2-p-ser96 (accessed [today's date]).

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