Is PHKB p.Arg103Ter (c.307C>T) pathogenic?

PHKB p.Arg103Ter (c.307C>T) is classified Pathogenic/Likely pathogenic in PHKB (ClinVar, Multiple submitters, 3 submitters; last evaluated 2025-03-24). Very rare (popmax 0.00834%, amr); Associated with glycogen storage disease IX.

What condition is associated with PHKB p.Arg103Ter (c.307C>T)?

PHKB p.Arg103Ter (c.307C>T) is associated with glycogen storage disease IX, glycogen storage disease IXb (ClinVar).

How common is PHKB p.Arg103Ter (c.307C>T) in the general population?

PHKB p.Arg103Ter (c.307C>T) is very rare (popmax 0.00834%, amr) (gnomAD).

PHKB p.Arg103Ter

c.307C>T · rs145166656 · VCV426940

Pathogenic/Likely pathogenic Multiple submitters

Classification

Pathogenic/Likely pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

Consequence

nonsense (stop-gain)

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.00834%, amr)

Conditions

glycogen storage disease IX

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	nonsense (stop-gain)	predicted loss-of-function
NMD	predicted	premature termination codon in exon 4 of 31
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.5	GERP 1.6, phastCons 1
Overall
CADD	40.0	PHRED · no single calibrated threshold — expert panels disagree

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00834% Admixed American · 5/59,982 alleles

Filtering AF 0.00323% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00207%

Overall 0.00156% 25/1,606,170 alleles · very rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00834%	11,996
African / African-American	0.00268%	37,368
East Asian	0.00223%	44,838
European (non-Finnish)	0.00136%	73,313
South Asian	0.0011%	90,904

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.Arg103Ter
Coding: c.307C>T
MANE Select: NM_000293
dbSNP: rs145166656
Type: single nucleotide variant
Location: chr16:47502992 (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 IX — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: glycogen storage disease IXb

Similar variants

PHKB p.Arg103Gln Uncertain significance ★★ ⚠ same residue
PHKB p.Arg103Leu Uncertain significance ★ ⚠ same residue
PHKB p.Arg103= 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

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-arg103ter (accessed [today's date]).

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