Is PHKB p.Ser27Ter (c.80C>G) pathogenic?

PHKB p.Ser27Ter (c.80C>G) is classified Pathogenic in PHKB (ClinVar, Single submitter, 1 submitter; last evaluated 2023-11-19). Very rare (popmax 8.63e-05%, nfe); Associated with glycogen storage disease IXb.

What condition is associated with PHKB p.Ser27Ter (c.80C>G)?

PHKB p.Ser27Ter (c.80C>G) is associated with glycogen storage disease IXb (ClinVar).

How common is PHKB p.Ser27Ter (c.80C>G) in the general population?

PHKB p.Ser27Ter (c.80C>G) is very rare (popmax 8.63e-05%, nfe) (gnomAD).

PHKB p.Ser27Ter

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

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

c.80C>G · rs769640225 · VCV2697311

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

nonsense (stop-gain)

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 8.63e-05%, nfe)

Conditions

glycogen storage disease IXb

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	nonsense (stop-gain)	predicted loss-of-function
NMD	predicted	premature termination codon in exon 2 of 31
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.6	GERP 2, phastCons 1
Overall
CADD	37.0	PHRED · no single calibrated threshold — expert panels disagree

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 8.63e-05% European (non-Finnish) · 1/1,159,200 alleles

Overall 6.97e-05% 1/1,434,640 alleles · very rare

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: PHKB
Protein: p.Ser27Ter
Coding: c.80C>G
MANE Select: NM_000293
dbSNP: rs769640225
Type: single nucleotide variant
Location: chr16:47497402 (GRCh38)
Gene constraint: LOEUF 0.792 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 87.06 · 6 PDB
Residue 27: the 'calmodulin-binding' region; a modified residue (phosphoserine)

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

Disease context

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

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

Inheritance: Autosomal recessive
Onset: Childhood

Similar variants

PHKB p.Ser27Leu Uncertain significance ★ ⚠ same residue
PHKB p.Ser27= Likely benign ★ same residue
PHKB c.1127-2A>G Pathogenic/Likely pathogenic ★★ same condition
PHKB c.1364-2A>G Pathogenic ★★ same condition
PHKB c.1972-2A>G Pathogenic/Likely pathogenic ★★ same condition
PHKB c.2427+965A>C Pathogenic/Likely pathogenic ★★ same condition
PHKB c.2896-1G>T Pathogenic ★★ same condition
PHKB c.306-2A>G 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/phkb-p-ser27ter (accessed [today's date]).

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