Is CSNK2B p.Met1Arg (c.2T>G) pathogenic?

CSNK2B p.Met1Arg (c.2T>G) is classified Pathogenic in CSNK2B (ClinVar, Single submitter, 1 submitter; last evaluated 2021-07-12). Very rare (popmax 0.00267%, afr).

How common is CSNK2B p.Met1Arg (c.2T>G) in the general population?

CSNK2B p.Met1Arg (c.2T>G) is very rare (popmax 0.00267%, afr) (gnomAD).

CSNK2B p.Met1Arg

c.2T>G · rs1562045237 · VCV1254603

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

start-loss

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.00267%, afr)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	start-loss	predicted loss-of-function in a LoF-intolerant gene
REVEL	0.496	indeterminate
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.9	GERP 1.9, phastCons 1
Overall
CADD	27.3	PHRED · no single calibrated threshold — expert panels disagree

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00267% African / African-American · 2/74,968 alleles

Filtering AF 0.00173% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00149%

Overall 0.00219% 32/1,460,032 alleles · very rare

Ancestry group	Frequency	1 in
Ashkenazi Jewishnot grpmax-eligible	0.00338%	29,544
African / African-Americangrpmax	0.00267%	37,484
European (non-Finnish)	0.00246%	40,640

Ashkenazi Jewish 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.Met1Arg
Coding: c.2T>G
MANE Select: NM_001320
dbSNP: rs1562045237
Type: single nucleotide variant
Location: chr6:31666833 (GRCh38)
Gene constraint: LOEUF 0.237 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 93.70 · 10 PDB

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

Similar variants

CSNK2B p.Met1Ile Pathogenic/Likely pathogenic ★★ same residue
CSNK2B p.Met1Val Pathogenic/Likely pathogenic ★★ same residue
CSNK2B p.Met1Lys Likely pathogenic ★ same residue
CSNK2B p.Met1Leu Conflicting classifications of pathogenicity ★ 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

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-met1arg (accessed [today's date]).

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