Is PHKB p.Phe378fs (c.1134del) pathogenic?

PHKB p.Phe378fs (c.1134del) is classified Pathogenic in PHKB (ClinVar, Single submitter, 1 submitter; last evaluated 2025-12-16). No allele count reported in gnomAD v4.1 (AN 1,510,462); Associated with glycogen storage disease IXb.

What condition is associated with PHKB p.Phe378fs (c.1134del)?

PHKB p.Phe378fs (c.1134del) is associated with glycogen storage disease IXb (ClinVar).

How common is PHKB p.Phe378fs (c.1134del) in the general population?

PHKB p.Phe378fs (c.1134del) is no allele count reported in gnomAD v4.1 (AN 1,510,462) (gnomAD).

PHKB p.Phe378fs

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.1134del · VCV4781269

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 1,510,462)

Conditions

glycogen storage disease IXb

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function
NMD	predicted	premature termination codon in exon 12 of 31
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 6.6	GERP 0.94, phastCons 1

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

Population frequency

gnomAD v4.1 · exomes + genomes

No allele count reported in gnomAD v4.1 (AN 1,510,462). This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: PHKB
Protein: p.Phe378fs
Coding: c.1134del
MANE Select: NM_000293
Type: Deletion
Location: chr16:47594140 (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 378: an α-helix

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.Phe378= Likely benign ★ same residue
PHKB p.Glu820fs Pathogenic/Likely pathogenic ★★ same condition
PHKB p.Val175fs Pathogenic/Likely pathogenic ★★ same condition
PHKB c.2427+964del Likely benign ★★ same condition
PHKB c.3144+34del Benign/Likely benign ★★ same condition
PHKB c.1363+1del Likely pathogenic ★ same condition
PHKB c.167-6_170del Likely pathogenic ★ same condition
PHKB c.2329_2336+5del 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-phe378fs (accessed [today's date]).

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