Is CSNK2B p.Arg111Pro (c.332G>C) pathogenic?

CSNK2B p.Arg111Pro (c.332G>C) is classified Pathogenic in CSNK2B (ClinVar, Multiple submitters, 3 submitters; last evaluated 2024-06-22). AlphaMissense: likely pathogenic (0.9996); Absent from gnomAD v4.1; Associated with CSNK2B-related disorder.

What condition is associated with CSNK2B p.Arg111Pro (c.332G>C)?

CSNK2B p.Arg111Pro (c.332G>C) is associated with CSNK2B-related disorder, Poirier-Bienvenu neurodevelopmental syndrome (ClinVar).

How common is CSNK2B p.Arg111Pro (c.332G>C) in the general population?

CSNK2B p.Arg111Pro (c.332G>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about CSNK2B p.Arg111Pro (c.332G>C)?

AlphaMissense predicts likely pathogenic (score 0.9996) — an in-silico prediction, not a clinical call.

CSNK2B p.Arg111Pro

c.332G>C · rs2151188333 · VCV1320202

Pathogenic Multiple submitters

Classification

Pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

AlphaMissense

likely pathogenic

0.9996 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

CSNK2B-related disorder

Computational evidence

Protein change
AlphaMissense	0.9996	likely pathogenic ✓ concordant with ClinVar · top 10% in CSNK2B
REVEL	0.951	strongly pathogenic-leaning
SaProt	LLR -14.64	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 1.2, phastCons 1
Regional constraint	o/e 0.39	unconstrained · MANE · 3,091 bp · p 1.2e-24 · regional, not allelic
Overall
CADD	33.0	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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: CSNK2B
Protein: p.Arg111Pro
Coding: c.332G>C
MANE Select: NM_001320
dbSNP: rs2151188333
Type: single nucleotide variant
Location: chr6:31669137 (GRCh38)
Gene constraint: LOEUF 0.237 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 93.70 · 10 PDB
Residue 111: a UniProt-annotated variant site (in pobinds; associated in cis with c-86); a UniProt-annotated variant site (in pobinds)

Full CSNK2B gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

CSNK2B-related disorder

Also linked: Poirier-Bienvenu neurodevelopmental syndrome

Similar variants

CSNK2B p.Arg111Cys Likely pathogenic same residue
CSNK2B p.Arg111Leu Likely pathogenic ★ same residue
CSNK2B c.175+1G>A Pathogenic/Likely pathogenic ★★ same condition
CSNK2B c.291+1G>A Pathogenic/Likely pathogenic ★★ same condition
CSNK2B c.291+1G>T Likely pathogenic ★★ same condition
CSNK2B c.292-2A>C Pathogenic/Likely pathogenic ★★ same condition
CSNK2B c.292-2A>G Pathogenic/Likely pathogenic ★★ same condition
CSNK2B c.557+1G>C 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/csnk2b-p-arg111pro (accessed [today's date]).

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