Is PHKB p.Arg482= (c.1446G>A) pathogenic?

PHKB p.Arg482= (c.1446G>A) is classified Benign/Likely benign in PHKB (ClinVar, Multiple submitters, 6 submitters; last evaluated 2026-01-28). Rare (popmax 0.594%, afr); Associated with glycogen storage disease IXb.

What condition is associated with PHKB p.Arg482= (c.1446G>A)?

PHKB p.Arg482= (c.1446G>A) is associated with glycogen storage disease IXb (ClinVar).

How common is PHKB p.Arg482= (c.1446G>A) in the general population?

PHKB p.Arg482= (c.1446G>A) is rare (popmax 0.594%, afr) (gnomAD).

PHKB p.Arg482=

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.1446G>A · rs149812232 · VCV389594

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 6 submitters

gnomAD v4.1

Rare

rare (popmax 0.594%, afr)

Conditions

glycogen storage disease IXb

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.036	GERP -3.5, phastCons 0.35
Overall
CADD	6.843	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.594% African / African-American · 441/74,282 alleles

Filtering AF 0.548% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.53%

Overall 0.0352% 556/1,577,330 alleles · rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.594%	168
Middle Eastern	0.316%	317
Admixed American	0.0551%	1,816
Remaining individualsnot grpmax-eligible	0.0489%	2,045
European (non-Finnish)	0.00279%	35,827
South Asian	0.00111%	90,390

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.Arg482=
Coding: c.1446G>A
MANE Select: NM_000293
dbSNP: rs149812232
Type: single nucleotide variant
Location: chr16:47610908 (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 482: a turn

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.Arg482fs Likely pathogenic ★ same residue
PHKB p.Arg482Lys Uncertain significance ★ ⚠ 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-arg482 (accessed [today's date]).

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