Is PHKB c.3003+12del pathogenic?

PHKB c.3003+12del is classified Likely benign in PHKB (ClinVar, Single submitter, 1 submitter; last evaluated 2026-01-31). Ultra-rare (popmax 0.0284%, amr); Associated with glycogen storage disease IXb.

What condition is associated with PHKB c.3003+12del?

PHKB c.3003+12del is associated with glycogen storage disease IXb (ClinVar).

How common is PHKB c.3003+12del in the general population?

PHKB c.3003+12del is ultra-rare (popmax 0.0284%, amr) (gnomAD).

PHKB c.3003+12del

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.

rs767601532 · VCV2078688

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.0284%, amr)

Conditions

glycogen storage disease IXb

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
Splice region	donor +12	near-intronic (+12 nt from the splice site)
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP -0.45	GERP -1.1
Non-coding constraint	Z 0.97	1 kb window · o/e 0.93 · regional · uncalibrated

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0284% Admixed American · 17/59,784 alleles

Filtering AF 0.0181% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0148%

Overall 0.00121% 17/1,407,472 alleles · ultra-rare exomes 17/1,255,170 · genomes 0/152,302 · joint denominator

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
Coding: c.3003+12del
MANE Select: NM_000293
dbSNP: rs767601532
Type: Deletion
Location: chr16:47696500 (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.Glu820fs Pathogenic/Likely pathogenic ★★ same condition
PHKB p.Val175fs Pathogenic/Likely pathogenic ★★ same condition
PHKB c.2427+964del Likely benign ★★ same condition
PHKB c.3144+34del Benign/Likely benign ★★ same condition
PHKB c.1363+1del Likely pathogenic ★ same condition
PHKB c.167-6_170del Likely pathogenic ★ same condition
PHKB c.2329_2336+5del Likely pathogenic ★ same condition
PHKB c.2427+1045del 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-c-3003-plus-12del (accessed [today's date]).

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