Is PHKB p.Asp106= (c.318T>C) pathogenic?

PHKB p.Asp106= (c.318T>C) is classified Benign in PHKB (ClinVar, Multiple submitters, 7 submitters; last evaluated 2026-02-04). Low-frequency (popmax 2.08%, nfe); Associated with glycogen storage disease IXb.

What condition is associated with PHKB p.Asp106= (c.318T>C)?

PHKB p.Asp106= (c.318T>C) is associated with glycogen storage disease IXb (ClinVar).

How common is PHKB p.Asp106= (c.318T>C) in the general population?

PHKB p.Asp106= (c.318T>C) is low-frequency (popmax 2.08%, nfe) (gnomAD).

PHKB p.Asp106=

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.318T>C · rs17738933 · VCV257178

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 7 submitters

gnomAD v4.1

Rare

low-frequency (popmax 2.08%, nfe)

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 0.62	GERP 0.52, phastCons 1
Overall
CADD	8.387	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 2.08% European (non-Finnish) · 24,456/1,177,510 alleles

Filtering AF 2.06% ClinGen BA1/BS1 input FAF95, joint · FAF99 2.05%

Overall 1.76% 28,419/1,611,428 alleles · low-frequency exomes 26,405/1,459,112 · genomes 2,014/152,316 · joint denominator

Ancestry group	Frequency	1 in
Finnishnot grpmax-eligible	3.44%	29
European (non-Finnish)grpmax	2.08%	48
Amishnot grpmax-eligible	1.43%	70
Remaining individualsnot grpmax-eligible	1.4%	71
Ashkenazi Jewishnot grpmax-eligible	0.686%	146
Middle Eastern	0.512%	195
Admixed American	0.377%	266
African / African-American	0.279%	359
South Asian	0.219%	457
East Asian	0.00669%	14,955

Finnish 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.Asp106=
Coding: c.318T>C
MANE Select: NM_000293
dbSNP: rs17738933
Type: single nucleotide variant
Location: chr16:47503003 (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 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
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-asp106 (accessed [today's date]).

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