Is PHKB p.Ala847= (c.2541G>A) pathogenic?

PHKB p.Ala847= (c.2541G>A) is classified Likely benign in PHKB (ClinVar, Single submitter, 1 submitter; last evaluated 2024-02-25). Ultra-rare (popmax 0.0111%, eas); Associated with glycogen storage disease IXb.

What condition is associated with PHKB p.Ala847= (c.2541G>A)?

PHKB p.Ala847= (c.2541G>A) is associated with glycogen storage disease IXb (ClinVar).

How common is PHKB p.Ala847= (c.2541G>A) in the general population?

PHKB p.Ala847= (c.2541G>A) is ultra-rare (popmax 0.0111%, eas) (gnomAD).

PHKB p.Ala847=

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.2541G>A · rs778551862 · VCV2722178

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.0111%, eas)

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	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP -7.9	GERP -5.8
Overall
CADD	1.022	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0111% East Asian · 5/44,890 alleles

Filtering AF 0.00434% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00276%

Overall 0.00167% 27/1,613,914 alleles · ultra-rare exomes 22/1,461,774 · genomes 5/152,140 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.0111%	8,978
African / African-American	0.004%	24,970
Remaining individualsnot grpmax-eligible	0.0032%	31,242
European (non-Finnish)	0.00136%	73,746
South Asian	0.0011%	91,082

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.Ala847=
Coding: c.2541G>A
MANE Select: NM_000293
dbSNP: rs778551862
Type: single nucleotide variant
Location: chr16:47669328 (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 847: 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.Ala847Val 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
PHKB p.Arg103Ter 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-ala847 (accessed [today's date]).

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