Is PHKB p.Pro298Ser (c.892C>T) pathogenic?

PHKB p.Pro298Ser (c.892C>T) is classified Uncertain significance in PHKB (ClinVar, Multiple submitters, 2 submitters; last evaluated 2024-06-06). AlphaMissense: likely benign (0.1539); Ultra-rare (popmax 0.049%, eas); Associated with glycogen storage disease IXb.

What condition is associated with PHKB p.Pro298Ser (c.892C>T)?

PHKB p.Pro298Ser (c.892C>T) is associated with glycogen storage disease IXb (ClinVar).

How common is PHKB p.Pro298Ser (c.892C>T) in the general population?

PHKB p.Pro298Ser (c.892C>T) is ultra-rare (popmax 0.049%, eas) (gnomAD).

What do computational predictors say about PHKB p.Pro298Ser (c.892C>T)?

AlphaMissense predicts likely benign (score 0.1539) — an in-silico prediction, not a clinical call.

PHKB p.Pro298Ser

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.892C>T · rs143805637 · VCV886774

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.1539 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.049%, eas)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

glycogen storage disease IXb

Computational evidence

Protein change
AlphaMissense	0.1539	likely benign
REVEL	0.487	indeterminate
SaProt	LLR -3.07	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.7	GERP 1.9, phastCons 1
Regional constraint	o/e 0.98	unconstrained · MANE · 238 kb · p 0.5 · regional, not allelic
Overall
CADD	21.6	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.049% East Asian · 22/44,874 alleles

Filtering AF 0.0332% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0279%

Overall 0.00143% 23/1,613,830 alleles · ultra-rare exomes 22/1,461,550 · genomes 1/152,280 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.049%	2,040
South Asian	0.0011%	91,066

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.Pro298Ser
Coding: c.892C>T
MANE Select: NM_000293
dbSNP: rs143805637
Type: single nucleotide variant
Location: chr16:47588926 (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 298: 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.Pro298Leu 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-pro298ser (accessed [today's date]).

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