Is CSNK2B p.Arg86His (c.257G>A) pathogenic?

CSNK2B p.Arg86His (c.257G>A) is classified Conflicting classifications of pathogenicity in CSNK2B (ClinVar, Conflicting submitters, 3 submitters; last evaluated 2025-08-04). AlphaMissense: likely pathogenic (0.9994); Very rare (popmax 0.00134%, afr); Associated with Poirier-Bienvenu neurodevelopmental syndrome.

What condition is associated with CSNK2B p.Arg86His (c.257G>A)?

CSNK2B p.Arg86His (c.257G>A) is associated with Poirier-Bienvenu neurodevelopmental syndrome (ClinVar).

How common is CSNK2B p.Arg86His (c.257G>A) in the general population?

CSNK2B p.Arg86His (c.257G>A) is very rare (popmax 0.00134%, afr) (gnomAD).

What do computational predictors say about CSNK2B p.Arg86His (c.257G>A)?

AlphaMissense predicts likely pathogenic (score 0.9994) — an in-silico prediction, not a clinical call.

CSNK2B p.Arg86His

c.257G>A · rs372125807 · VCV2502649

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 3 submitters

AlphaMissense

likely pathogenic

0.9994 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00134%, afr)

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Poirier-Bienvenu neurodevelopmental syndrome

Computational evidence

Protein change
AlphaMissense	0.9994	likely pathogenic · top 10% in CSNK2B
REVEL	0.894	moderately pathogenic-leaning
SaProt	LLR -16.72	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 0.67, 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

Grpmax group 0.00134% African / African-American · 1/74,906 alleles

Filtering AF 6.8e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.9e-05%

Overall 0.00031% 5/1,612,936 alleles · very rare

Ancestry group	Frequency	1 in
Finnishnot grpmax-eligible	0.00159%	62,932
African / African-Americangrpmax	0.00134%	74,906
European (non-Finnish)	0.000254%	393,349

Finnish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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: CSNK2B
Protein: p.Arg86His
Coding: c.257G>A
MANE Select: NM_001320
dbSNP: rs372125807
Type: single nucleotide variant
Location: chr6:31668620 (GRCh38)
Gene constraint: LOEUF 0.237 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 93.70 · 10 PDB
Residue 86: a UniProt-annotated variant site (in pobinds; associated in cis with c-86); a UniProt-annotated variant site (in pobinds; uncertain significance; associated in cis with 5-e--r-215 del); an α-helix

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

Disease context

Poirier-Bienvenu neurodevelopmental syndrome — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

CSNK2B p.Arg86Pro Likely pathogenic ★ same residue
CSNK2B p.Arg86Cys Conflicting classifications of pathogenicity ★ ⚠ 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-arg86his (accessed [today's date]).

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