Is PHKB p.Pro1014= (c.3042C>T) pathogenic?

PHKB p.Pro1014= (c.3042C>T) is classified Likely benign in PHKB (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-09-06). Ultra-rare (popmax 0.0447%, eas); Associated with glycogen storage disease IXb.

What condition is associated with PHKB p.Pro1014= (c.3042C>T)?

PHKB p.Pro1014= (c.3042C>T) is associated with glycogen storage disease IXb (ClinVar).

How common is PHKB p.Pro1014= (c.3042C>T) in the general population?

PHKB p.Pro1014= (c.3042C>T) is ultra-rare (popmax 0.0447%, eas) (gnomAD).

PHKB p.Pro1014=

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.3042C>T · rs149234185 · VCV668344

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0447%, eas)

Conditions

glycogen storage disease IXb

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -0.75	GERP -4.7, phastCons 0.019
Overall
CADD	9.141	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0447% East Asian · 20/44,772 alleles

Filtering AF 0.0295% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0247%

Overall 0.00335% 54/1,611,296 alleles · ultra-rare exomes 51/1,459,302 · genomes 3/151,994 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.0447%	2,239
Middle Eastern	0.0165%	6,050
Remaining individualsnot grpmax-eligible	0.0032%	31,202
European (non-Finnish)	0.00246%	40,613
South Asian	0.0022%	45,514

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.Pro1014=
Coding: c.3042C>T
MANE Select: NM_000293
dbSNP: rs149234185
Type: single nucleotide variant
Location: chr16:47698486 (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

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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
PHKB p.Arg429Ter 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-pro1014 (accessed [today's date]).

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