Is PHKB p.Thr519fs (c.1555dup) pathogenic?

PHKB p.Thr519fs (c.1555dup) is classified Pathogenic in PHKB (ClinVar, Single submitter, 1 submitter; last evaluated 2025-01-12). Very rare (popmax 0.00167%, amr); Associated with glycogen storage disease IXb.

What condition is associated with PHKB p.Thr519fs (c.1555dup)?

PHKB p.Thr519fs (c.1555dup) is associated with glycogen storage disease IXb (ClinVar).

How common is PHKB p.Thr519fs (c.1555dup) in the general population?

PHKB p.Thr519fs (c.1555dup) is very rare (popmax 0.00167%, amr) (gnomAD).

PHKB p.Thr519fs

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.1555dup · VCV3622438

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.00167%, amr)

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 16 of 31
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 7.6	GERP 2.7, phastCons 1

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00167% Admixed American · 1/60,022 alleles

Overall 6.88e-05% 1/1,454,248 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.Thr519fs
Coding: c.1555dup
MANE Select: NM_000293
Type: Duplication
Location: chr16:47641636 (GRCh38)
Gene constraint: LOEUF 0.792 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 87.06 · 6 PDB

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.Thr519= Likely benign ★ same residue
PHKB p.Asn422fs Pathogenic ★★ same condition
PHKB c.3144+33_3144+34dup Benign ★★ same condition
PHKB c.594+1dup Likely pathogenic ★ same condition
PHKB p.Asp318Ter Likely pathogenic ★ same condition
PHKB p.Gln389fs Pathogenic ★ same condition
PHKB p.Gln603fs Pathogenic ★ same condition
PHKB p.Gln809fs 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-thr519fs (accessed [today's date]).

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