Is PHKB p.Ala601= (c.1803G>A) pathogenic?

PHKB p.Ala601= (c.1803G>A) is classified Likely benign in PHKB (ClinVar, Multiple submitters, 3 submitters; last evaluated 2026-01-12). Rare (popmax 0.136%, afr); Associated with glycogen storage disease IXb.

What condition is associated with PHKB p.Ala601= (c.1803G>A)?

PHKB p.Ala601= (c.1803G>A) is associated with glycogen storage disease IXb (ClinVar).

How common is PHKB p.Ala601= (c.1803G>A) in the general population?

PHKB p.Ala601= (c.1803G>A) is rare (popmax 0.136%, afr) (gnomAD).

PHKB p.Ala601=

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.1803G>A · rs35690654 · VCV257172

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

gnomAD v4.1

Rare

rare (popmax 0.136%, 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 -0.94	GERP -5.8
Overall
CADD	6.802	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.136% African / African-American · 101/74,460 alleles

Filtering AF 0.114% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.106%

Overall 0.00901% 143/1,586,392 alleles · rare exomes 77/1,434,204 · genomes 66/152,188 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.136%	737
Admixed American	0.0167%	5,997
Middle Eastern	0.0166%	6,018
Remaining individualsnot grpmax-eligible	0.0146%	6,838
East Asian	0.00224%	44,738
South Asian	0.00221%	45,250
European (non-Finnish)	0.00165%	60,790

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.Ala601=
Coding: c.1803G>A
MANE Select: NM_000293
dbSNP: rs35690654
Type: single nucleotide variant
Location: chr16:47650549 (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 601: 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.Ala601Val Uncertain significance ★ ⚠ same residue
PHKB p.Ala601Glu 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-ala601 (accessed [today's date]).

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