Is PHKB p.Pro1059Ser (c.3175C>T) pathogenic?

PHKB p.Pro1059Ser (c.3175C>T) is classified Uncertain significance in PHKB (ClinVar, Multiple submitters, 3 submitters; last evaluated 2024-02-21). AlphaMissense: likely benign (0.1482); Ultra-rare (popmax 0.0557%, eas); Associated with Inborn genetic diseases.

What condition is associated with PHKB p.Pro1059Ser (c.3175C>T)?

PHKB p.Pro1059Ser (c.3175C>T) is associated with Inborn genetic diseases, glycogen storage disease IXb (ClinVar).

How common is PHKB p.Pro1059Ser (c.3175C>T) in the general population?

PHKB p.Pro1059Ser (c.3175C>T) is ultra-rare (popmax 0.0557%, eas) (gnomAD).

What do computational predictors say about PHKB p.Pro1059Ser (c.3175C>T)?

AlphaMissense predicts likely benign (score 0.1482) — an in-silico prediction, not a clinical call.

PHKB p.Pro1059Ser

c.3175C>T · rs746809041 · VCV1003568

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

AlphaMissense

likely benign

0.1482 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0557%, eas)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.1482	likely benign
REVEL	0.572	indeterminate
SaProt	LLR -10.91	damaging
⇒ SaProt calls this damaging; AlphaMissense does not; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 6	GERP 2.4, phastCons 1
Regional constraint	o/e 0.98	unconstrained · MANE · 238 kb · p 0.5 · regional, not allelic
Overall
CADD	22.1	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0557% East Asian · 25/44,880 alleles

Filtering AF 0.0387% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.033%

Overall 0.00167% 27/1,613,932 alleles · ultra-rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.0557%	1,795
South Asian	0.0022%	45,539

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.Pro1059Ser
Coding: c.3175C>T
MANE Select: NM_000293
dbSNP: rs746809041
Type: single nucleotide variant
Location: chr16:47699259 (GRCh38)
Gene constraint: LOEUF 0.792 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 87.06 · 6 PDB
Residue 1059: a β-strand

Full PHKB gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: glycogen storage disease IXb

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-pro1059ser (accessed [today's date]).

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