Is PHKB p.Ile450Phe (c.1348A>T) pathogenic?

PHKB p.Ile450Phe (c.1348A>T) is classified Uncertain significance in PHKB (ClinVar, Single submitter, 1 submitter; last evaluated 2024-10-18). AlphaMissense: ambiguous (0.4058); Absent from gnomAD v4.1; Associated with glycogen storage disease IXb.

What condition is associated with PHKB p.Ile450Phe (c.1348A>T)?

PHKB p.Ile450Phe (c.1348A>T) is associated with glycogen storage disease IXb (ClinVar).

How common is PHKB p.Ile450Phe (c.1348A>T) in the general population?

PHKB p.Ile450Phe (c.1348A>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about PHKB p.Ile450Phe (c.1348A>T)?

AlphaMissense predicts ambiguous (score 0.4058) — an in-silico prediction, not a clinical call.

PHKB p.Ile450Phe

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.1348A>T · rs757003045 · VCV2058194

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.4058 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

1/2 damaging

REVEL, SaProt · AlphaMissense no call

Conditions

glycogen storage disease IXb

Computational evidence

Protein change
AlphaMissense	0.4058	ambiguous
REVEL	0.92	moderately pathogenic-leaning
SaProt	LLR -7.33	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 11	GERP 1.2, phastCons 1
Regional constraint	o/e 0.98	unconstrained · MANE · 238 kb · p 0.5 · regional, not allelic
Overall
CADD	25.4	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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: PHKB
Protein: p.Ile450Phe
Coding: c.1348A>T
MANE Select: NM_000293
dbSNP: rs757003045
Type: single nucleotide variant
Location: chr16:47596516 (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 450: 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.Ile450= Conflicting classifications of pathogenicity ★ 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-ile450phe (accessed [today's date]).

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