Is PBK p.Ser52Phe (c.155C>T) pathogenic?

PBK p.Ser52Phe (c.155C>T) is classified Uncertain significance in PBK (ClinVar, Single submitter, 1 submitter; last evaluated 2025-05-19). AlphaMissense: ambiguous (0.5344); Very rare (popmax 0.00237%, eas).

How common is PBK p.Ser52Phe (c.155C>T) in the general population?

PBK p.Ser52Phe (c.155C>T) is very rare (popmax 0.00237%, eas) (gnomAD).

What do computational predictors say about PBK p.Ser52Phe (c.155C>T)?

AlphaMissense predicts ambiguous (score 0.5344) — an in-silico prediction, not a clinical call.

PBK p.Ser52Phe

c.155C>T · rs1443900189 · VCV2266018

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.5344 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00237%, eas)

Computational evidence

Protein change
AlphaMissense	0.5344	ambiguous
REVEL	0.465	indeterminate
SaProt	LLR -8.77	tolerated
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 1.8, phastCons 1
Regional constraint	o/e 0.98	unconstrained · MANE · 23 kb · p 0.7 · regional, not allelic
Overall
CADD	28.6	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 0.00237% East Asian · 1/42,258 alleles

Overall 0.000134% 2/1,488,200 alleles · very rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00237%	42,258
African / African-American	0.00143%	70,024

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: PBK
Protein: p.Ser52Phe
Coding: c.155C>T
MANE Select: NM_018492
dbSNP: rs1443900189
Type: single nucleotide variant
Location: chr8:27823203 (GRCh38)
Gene constraint: LOEUF 1.057 · pLI 0.43 (gnomAD)
Structure: AlphaFold pLDDT 84.66 · 1 PDB
Residue 52: the protein kinase domain

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

Similar variants

PBK p.Ala151Glu Uncertain significance ★ ⚠ same type
PBK p.Arg130Gln Uncertain significance ★ ⚠ same type
PBK p.Cys112Tyr Uncertain significance ★ ⚠ same type
PBK p.Cys70Arg Uncertain significance ★ ⚠ same type
PBK p.Gln159Leu Uncertain significance ★ ⚠ same type
PBK p.Ile127Thr Uncertain significance ★ ⚠ same type
PBK p.Leu113Phe Uncertain significance ★ ⚠ same type
PBK p.Leu164Phe Uncertain significance ★ ⚠ same type

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/pbk-p-ser52phe (accessed [today's date]).

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