Is PHKB p.Arg429Ter (c.1285C>T) pathogenic?

PHKB p.Arg429Ter (c.1285C>T) is classified Pathogenic in PHKB (ClinVar, Multiple submitters, 4 submitters; last evaluated 2025-08-13). Ultra-rare (popmax 0.0133%, nfe); Associated with PHKB-related disorder.

What condition is associated with PHKB p.Arg429Ter (c.1285C>T)?

PHKB p.Arg429Ter (c.1285C>T) is associated with PHKB-related disorder, glycogen storage disease IXb, glycogen storage disease IX (ClinVar).

How common is PHKB p.Arg429Ter (c.1285C>T) in the general population?

PHKB p.Arg429Ter (c.1285C>T) is ultra-rare (popmax 0.0133%, nfe) (gnomAD).

PHKB p.Arg429Ter

c.1285C>T · rs563345848 · VCV1699565

Pathogenic Multiple submitters

Classification

Pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

Consequence

nonsense (stop-gain)

predicted LoF

gnomAD v4.1

Rare

ultra-rare (popmax 0.0133%, nfe)

Conditions

PHKB-related disorder

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 13 of 31
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 1.4	GERP -0.18, phastCons 1
Overall
CADD	35.0	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 0.0133% European (non-Finnish) · 157/1,179,528 alleles

Filtering AF 0.0116% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0109%

Overall 0.0106% 171/1,613,566 alleles · ultra-rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.0133%	7,513
Admixed American	0.00833%	12,003
African / African-American	0.004%	25,009
South Asian	0.00329%	30,356
Remaining individualsnot grpmax-eligible	0.0032%	31,244
East Asian	0.00223%	44,872

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.Arg429Ter
Coding: c.1285C>T
MANE Select: NM_000293
dbSNP: rs563345848
Type: single nucleotide variant
Location: chr16:47596453 (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

PHKB-related disorder

Also linked: glycogen storage disease IXb glycogen storage disease IX

Similar variants

PHKB p.Arg429Gln Uncertain significance ★★ ⚠ 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-arg429ter (accessed [today's date]).

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