Is PHKB p.Arg630Trp (c.1888C>T) pathogenic?

PHKB p.Arg630Trp (c.1888C>T) is classified Uncertain significance in PHKB (ClinVar, Single submitter, 1 submitter; last evaluated 2021-12-25). AlphaMissense: ambiguous (0.414); Very rare (popmax 0.00134%, afr); Associated with glycogen storage disease IXb.

What condition is associated with PHKB p.Arg630Trp (c.1888C>T)?

PHKB p.Arg630Trp (c.1888C>T) is associated with glycogen storage disease IXb (ClinVar).

How common is PHKB p.Arg630Trp (c.1888C>T) in the general population?

PHKB p.Arg630Trp (c.1888C>T) is very rare (popmax 0.00134%, afr) (gnomAD).

What do computational predictors say about PHKB p.Arg630Trp (c.1888C>T)?

AlphaMissense predicts ambiguous (score 0.414) — an in-silico prediction, not a clinical call.

PHKB p.Arg630Trp

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.1888C>T · rs747479623 · VCV1924320

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.414 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00134%, afr)

Missense predictors

1/2 damaging

REVEL, SaProt · AlphaMissense no call

Conditions

glycogen storage disease IXb

Computational evidence

Protein change
AlphaMissense	0.414	ambiguous
REVEL	0.742	pathogenic-leaning
SaProt	LLR -8.26	tolerated
⇒ REVEL calls this damaging; SaProt does not; AlphaMissense makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.91	GERP 1.2, phastCons 1
Regional constraint	o/e 0.98	unconstrained · MANE · 238 kb · p 0.5 · regional, not allelic
Overall
CADD	26.5	PHRED · no single calibrated threshold — expert panels disagree

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00134% African / African-American · 1/74,842 alleles

Filtering AF 8e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 5.4e-05%

Overall 0.00048% 7/1,458,732 alleles · very rare

Ancestry group	Frequency	1 in
Remaining individualsnot grpmax-eligible	0.0032%	31,203
African / African-Americangrpmax	0.00134%	74,842
European (non-Finnish)	0.00034%	294,312

Remaining individuals shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Arg630Trp
Coding: c.1888C>T
MANE Select: NM_000293
dbSNP: rs747479623
Type: single nucleotide variant
Location: chr16:47650838 (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 630: 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

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PHKB c.306-2A>G Pathogenic/Likely pathogenic ★★ same condition
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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-arg630trp (accessed [today's date]).

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