Is PHKB p.Val15= (c.45C>T) pathogenic?

PHKB p.Val15= (c.45C>T) is classified Likely benign in PHKB (ClinVar, Single submitter, 1 submitter; last evaluated 2024-09-14). Ultra-rare (popmax 0.0253%, sas); Associated with glycogen storage disease IXb.

What condition is associated with PHKB p.Val15= (c.45C>T)?

PHKB p.Val15= (c.45C>T) is associated with glycogen storage disease IXb (ClinVar).

How common is PHKB p.Val15= (c.45C>T) in the general population?

PHKB p.Val15= (c.45C>T) is ultra-rare (popmax 0.0253%, sas) (gnomAD).

PHKB p.Val15=

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.45C>T · rs573650598 · VCV2898934

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.0253%, sas)

Conditions

glycogen storage disease IXb

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · C>A here scores Δ0.75 · evaluated, not missing
Constraint at this position
Conservation	phyloP 0.66	GERP -0.49, phastCons 0.98
Overall
CADD	12.64	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0253% South Asian · 23/91,054 alleles

Filtering AF 0.0172% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0146%

Overall 0.00161% 26/1,613,232 alleles · ultra-rare exomes 24/1,460,920 · genomes 2/152,312 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0253%	3,959
Middle Eastern	0.0168%	5,946
European (non-Finnish)	0.00017%	589,904

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.Val15=
Coding: c.45C>T
MANE Select: NM_000293
dbSNP: rs573650598
Type: single nucleotide variant
Location: chr16:47461395 (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 15: the 'calmodulin-binding' region

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 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
PHKB p.Arg103Ter Pathogenic/Likely pathogenic ★★ same condition
PHKB p.Arg429Ter 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-val15 (accessed [today's date]).

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