# NM_001320.7(CSNK2B):c.516C>T (p.Pro172=)

https://sugi.bio/variant/csnk2b-p-pro172

## Summary

**CSNK2B p.Pro172= (c.516C>T)** is classified **Likely benign** in CSNK2B (ClinVar, Single submitter, 1 submitter; last evaluated 2024-08-01). Very rare (popmax 0.0022%, sas).

**At a glance:** Likely benign · review: Single submitter · 1 submitter · very rare (popmax 0.0022%, sas)

## For patients & families {#patients}

This is a change in the CSNK2B gene that is classified as likely benign — not considered disease-causing, submitted by 1 submitter.

*Reference information, not medical advice, and not a prediction for any individual. A genetic counselor or clinician can interpret what it means for you and your family.*

**Support & next steps:** [Find a genetic counselor (NSGC)](https://findageneticcounselor.nsgc.org/).

## Identity {#identity}

| Field | Value |
| --- | --- |
| Gene | [CSNK2B](https://sugi.bio/atlas/gene/CSNK2B/) |
| Protein change (HGVS p.) | p.Pro172= |
| Coding change (HGVS c.) | c.516C>T |
| MANE Select transcript | [NM_001320](https://www.ncbi.nlm.nih.gov/nuccore/NM_001320) |
| Variant type | single nucleotide variant |
| Location | chr6:31669467-31669467 (GRCh38) |
| ClinVar | [VCV3341901](https://www.ncbi.nlm.nih.gov/clinvar/variation/3341901/) |

**All HGVS expressions:** `NC_000006.11:g.31637244C>T`, `NC_000006.12:g.31669467C>T`, `NM_001282385.2:c.507C>T`, `NM_001320.7:c.516C>T`

## Computational & population evidence {#evidence}

**Concordance:** Mixed / partial computational evidence (see below).

- **Missense predictors (AlphaMissense/REVEL/SaProt) do not apply** to this variant type — they score amino-acid substitutions only. For non-missense variants the computational signal comes from conservation (below), not from a missing predictor score.
- Conservation: phyloP -7.527, GERP -4.89 — fast-evolving / accelerated position
- CADD: **PHRED 6.526**. No single ClinGen-calibrated threshold exists and the expert panels that use CADD disagree — GUCY2D/AIPL1 require ≥ 20.0 for an untranslated-region variant, ABCA4 ≥ 28.1 for a synonymous or indel variant, the Pulmonary Hypertension panel imports Pejaver 2022's missense-calibrated numbers, and the Antibody Deficiencies panel declines CADD entirely for PIK3CD. CADD v1.7 also incorporates Zoonomia phyloP, so it partly re-expresses the conservation above. *Descriptive; no threshold applied.*
- SpliceAI: **not assessed** — no allele at this position is in our SpliceAI release, either because it lies outside the scored MANE transcript scope or because every allele is below Δ0.2. We cannot tell which, so this claims neither; absence is not evidence against a splicing effect.
- Population frequency (gnomAD v4.1): grpmax **0.0022%** (sas) · FAF95 0.000878% · FAF99 0.000717% · 2/91,084 in the highest group · 19/1,612,848 alleles overall — very rare (popmax 0.0022%, sas).

| Ancestry group | Allele frequency | 1 in |
| --- | --- | --- |
| South Asian (grpmax) | 0.0022% | 45,542 |
| European (non-Finnish) | 0.00144% | 69,412 |

*Computational predictors are not independent (ClinGen Variant Classification guidance): AlphaMissense (Cheng et al. 2023) carries the ACMG weight for missense and conservation (phyloP/GERP/phastCons) for non-missense; REVEL (Pejaver-2022 calibrated strength bands) and SaProt (Su et al. 2023, structure-aware, ClinVar-independent protein language model, raw LLR) are shown as orthogonal agreement signals, not additive. For frequency, the gnomAD v4.1 grpmax filtering allele frequency (FAF95) is ClinGen's designated BA1/BS1 input (gnomAD v4 guidance v3.0, June 2025); BA1/BS1 thresholds are disease-specific, not a blanket 5%. Predictions, not a clinical determination.*

## Gene constraint & dosage {#gene-context}

**CSNK2B** population constraint: LOEUF 0.237, pLI 0.99996, missense-Z 3.7843. *Lower LOEUF and higher pLI indicate a gene that tolerates loss-of-function poorly; ClinGen dosage is the curated haploinsufficiency call.*

Curated gene–disease validity (ClinGen):

- **Poirier-Bienvenu neurodevelopmental syndrome** — Definitive (AD)

## Protein context {#protein}

Residue **172** lies in a UniProt-annotated variant site (in pobinds; associated in cis with c-86); an α-helix.

AlphaFold model confidence (whole protein): pLDDT 93.70, 87% of residues very-high.

**10 experimental structure(s)** (PDB): [1DS5](https://www.rcsb.org/structure/1DS5), [1JWH](https://www.rcsb.org/structure/1JWH), [1QF8](https://www.rcsb.org/structure/1QF8), [3EED](https://www.rcsb.org/structure/3EED), [4DGL](https://www.rcsb.org/structure/4DGL), [4MD7](https://www.rcsb.org/structure/4MD7) — incl. mutant structure 3EED.

## What this gene does {#gene-function}

*Describes the biological roles of CSNK2B (the gene this variant disrupts) — not effects measured for this specific variant. A damaging variant is expected to affect these functions and pathways; the degree depends on the variant.*

**How this variant is thought to act:** CSNK2B's established molecular role includes chromatin binding. In Reactome, CSNK2B is annotated in disease pathway(s) including **Maturation of hRSV A proteins**.

**Disease mechanism (Reactome):** CSNK2B loss or alteration is curated in [Maturation of hRSV A proteins](https://reactome.org/content/detail/R-HSA-9828806).

### Pathways affected {#pathways}

CSNK2B participates in **16 Reactome pathways** (⚕ = disease pathway):

| Pathway (Reactome) | Evidence |
| --- | --- |
| ⚕ [Maturation of hRSV A proteins](https://reactome.org/content/detail/R-HSA-9828806) | curated |
| [Condensation of Prometaphase Chromosomes](https://reactome.org/content/detail/R-HSA-2514853) | curated |
| [Cooperation of PDCL (PhLP1) and TRiC/CCT in G-protein beta folding](https://reactome.org/content/detail/R-HSA-6814122) | curated |
| [Neutrophil degranulation](https://reactome.org/content/detail/R-HSA-6798695) | curated |
| [RUNX1 interacts with co-factors whose precise effect on RUNX1 targets is not known](https://reactome.org/content/detail/R-HSA-8939243) | curated |
| [Receptor Mediated Mitophagy](https://reactome.org/content/detail/R-HSA-8934903) | curated |
| [Regulation of CDH1 posttranslational processing and trafficking to plasma membrane](https://reactome.org/content/detail/R-HSA-9768727) | curated |
| [Regulation of PTEN stability and activity](https://reactome.org/content/detail/R-HSA-8948751) | curated |
| [Regulation of TP53 Activity through Phosphorylation](https://reactome.org/content/detail/R-HSA-6804756) | curated |
| [SPOP-mediated proteasomal degradation of PD-L1(CD274)](https://reactome.org/content/detail/R-HSA-9929491) | curated |
| [Signal transduction by L1](https://reactome.org/content/detail/R-HSA-445144) | curated |
| [Synthesis of PC](https://reactome.org/content/detail/R-HSA-1483191) | curated |
| [WNT mediated activation of DVL](https://reactome.org/content/detail/R-HSA-201688) | curated |
| [KEAP1-NFE2L2 pathway](https://reactome.org/content/detail/R-HSA-9755511) | electronic |
| [Phosphorylation and nuclear translocation of BMAL1 (ARNTL) and CLOCK](https://reactome.org/content/detail/R-HSA-9931529) | electronic |
| [Phosphorylation and nuclear translocation of the CRY:PER:kinase complex](https://reactome.org/content/detail/R-HSA-9931530) | electronic |

### Molecular function & processes (GO — experimentally supported) {#go}

**Molecular function:** chromatin binding, protein serine/threonine kinase activity, signaling receptor binding, protein domain specific binding, protein-macromolecule adaptor activity, identical protein binding.

**Biological process:** negative regulation of proteasomal ubiquitin-dependent protein catabolic process, positive regulation of activin receptor signaling pathway, adiponectin-activated signaling pathway, negative regulation of blood vessel endothelial cell migration, positive regulation of SMAD protein signal transduction, endothelial tube morphogenesis.

## Clinical significance {#significance}

**Likely benign** — review status Single submitter *(criteria provided, single submitter)*, last evaluated 2024-08-01.

**Submitter consensus:** unanimous (1/1 Likely benign).

### Submitter classifications {#submitters}

| Submitter | Classification | Review | Method | Date |
| --- | --- | --- | --- | --- |
| CeGaT Center for Human Genetics Tuebingen | Likely benign | criteria provided, single submitter | clinical testing | 2024-08-01 |

**Reported phenotype names (ClinVar):** not provided, none provided.

## Similar variants {#similar}

Related CSNK2B variant pages (same residue, condition, or type): [CSNK2B p.Pro172Arg](/variant/csnk2b-p-pro172arg), [CSNK2B c.175+1G>A](/variant/csnk2b-c-175-plus-1g-a), [CSNK2B c.291+1G>A](/variant/csnk2b-c-291-plus-1g-a), [CSNK2B c.291+1G>T](/variant/csnk2b-c-291-plus-1g-t), [CSNK2B c.292-2A>C](/variant/csnk2b-c-292-minus-2a-c), [CSNK2B c.292-2A>G](/variant/csnk2b-c-292-minus-2a-g), [CSNK2B c.292-2A>T](/variant/csnk2b-c-292-minus-2a-t), [CSNK2B c.367+1G>C](/variant/csnk2b-c-367-plus-1g-c).

### Data sources & attribution {#sources}

ClinVar (NCBI — public domain, built 2026-10-11); gnomAD v4.1 (Broad Institute, built 2026-10-06); AlphaMissense (Cheng et al. 2023, © Google DeepMind — CC BY 4.0, built 2026-01-27); REVEL (Ioannidis et al. 2016 — ODbL, built 2026-07-13); SaProt (Su et al. 2023 — MIT, built 2026-07-14); SpliceAI (Illumina — free for non-commercial use, built 2026-10-13); CADD (Rentzsch et al. 2019, University of Washington — free for non-commercial use, built 2026-10-10); Conservation (phyloP/phastCons/GERP) (UCSC hg38 470-way mammal (Hiller Lab) + Ensembl Compara, built 2026-07-12); gnomAD Non-coding Constraint (Gnocchi) (Chen et al. 2024, Broad Institute — CC0, built 2026-10-11); gnomAD Regional Missense Constraint (Broad Institute — CC0, built 2026-10-13); Pangolin (Zeng & Li 2022 — CC BY 4.0, built 2026-10-11); Repeat regions (UCSC — RepeatMasker, TRF, segmental duplications, built 2026-10-11); ClinGen (ClinGen, built 2026-09-22); UniProt (CC BY 4.0); Reactome / GO (CC BY 4.0, built 2026-09-23); MaveDB (per-record license, built 2026-10-11); CIViC (CC0, built 2026-09-22); Orphanet (Orphanet, built 2026-06-12)

*Primary record: NCBI ClinVar (variation 3341901). Classifications reflect these databases as of the page's build date and may change. Free reference use — not medical advice; consult the primary submitters and a clinician.*