Is PHKB p.Pro366Leu (c.1097C>T) pathogenic?

PHKB p.Pro366Leu (c.1097C>T) is classified Uncertain significance in PHKB (ClinVar, Single submitter, 1 submitter; last evaluated 2022-12-03). AlphaMissense: likely pathogenic (0.946); No allele count reported in gnomAD v4.1 (AN 1,494,184); Associated with glycogen storage disease IXb.

What condition is associated with PHKB p.Pro366Leu (c.1097C>T)?

PHKB p.Pro366Leu (c.1097C>T) is associated with glycogen storage disease IXb (ClinVar).

How common is PHKB p.Pro366Leu (c.1097C>T) in the general population?

PHKB p.Pro366Leu (c.1097C>T) is no allele count reported in gnomAD v4.1 (AN 1,494,184) (gnomAD).

What do computational predictors say about PHKB p.Pro366Leu (c.1097C>T)?

AlphaMissense predicts likely pathogenic (score 0.946) — an in-silico prediction, not a clinical call.

PHKB p.Pro366Leu

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.1097C>T · rs2506392262 · VCV2960296

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.946 · ACMG-weighted

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 1,494,184)

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

glycogen storage disease IXb

Computational evidence

Protein change
AlphaMissense	0.946	likely pathogenic
REVEL	0.901	moderately pathogenic-leaning
SaProt	LLR -14.80	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
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	26.2	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — 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

No allele count reported in gnomAD v4.1 (AN 1,494,184). This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: PHKB
Protein: p.Pro366Leu
Coding: c.1097C>T
MANE Select: NM_000293
dbSNP: rs2506392262
Type: single nucleotide variant
Location: chr16:47593528 (GRCh38)
Gene constraint: LOEUF 0.792 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 87.06 · 6 PDB

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.Pro366= Likely benign ★ 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-pro366leu (accessed [today's date]).

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