Is CSNK2B p.Phe34Cys (c.101T>G) pathogenic?

CSNK2B p.Phe34Cys (c.101T>G) is classified Likely pathogenic in CSNK2B (ClinVar, Single submitter, 1 submitter; last evaluated 2021-09-15). AlphaMissense: likely pathogenic (0.9999); Very rare (popmax 8.76e-05%, nfe).

How common is CSNK2B p.Phe34Cys (c.101T>G) in the general population?

CSNK2B p.Phe34Cys (c.101T>G) is very rare (popmax 8.76e-05%, nfe) (gnomAD).

What do computational predictors say about CSNK2B p.Phe34Cys (c.101T>G)?

AlphaMissense predicts likely pathogenic (score 0.9999) — an in-silico prediction, not a clinical call.

CSNK2B p.Phe34Cys

c.101T>G · rs1374628000 · VCV1275774

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9999 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 8.76e-05%, nfe)

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.9999	likely pathogenic ✓ concordant with ClinVar · top 10% in CSNK2B
REVEL	0.692	pathogenic-leaning
SaProt	LLR -14.53	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 7.9	GERP 1.6, phastCons 1
Regional constraint	o/e 0.39	unconstrained · MANE · 3,091 bp · p 1.2e-24 · regional, not allelic
Overall
CADD	32.0	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 8.76e-05% European (non-Finnish) · 1/1,141,416 alleles

Overall 7.28e-05% 1/1,374,480 alleles · very rare

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.Phe34Cys
Coding: c.101T>G
MANE Select: NM_001320
dbSNP: rs1374628000
Type: single nucleotide variant
Location: chr6:31667896 (GRCh38)
Gene constraint: LOEUF 0.237 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 93.70 · 10 PDB
Residue 34: a UniProt-annotated variant site (in pobinds; associated in cis with c-86); an α-helix

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

Similar variants

CSNK2B p.Phe34Leu Uncertain significance ★ ⚠ same residue
CSNK2B p.Phe34fs Likely pathogenic ★ same residue
CSNK2B c.175+1G>A Pathogenic/Likely pathogenic ★★ same type
CSNK2B c.291+1G>A Pathogenic/Likely pathogenic ★★ same type
CSNK2B c.291+1G>T Likely pathogenic ★★ same type
CSNK2B c.292-2A>C Pathogenic/Likely pathogenic ★★ same type
CSNK2B c.292-2A>G Pathogenic/Likely pathogenic ★★ same type
CSNK2B c.292-2A>T Pathogenic/Likely pathogenic ★★ 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/csnk2b-p-phe34cys (accessed [today's date]).

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