Is CSNK2A1 p.Pro366Ser (c.1096C>T) pathogenic?

CSNK2A1 p.Pro366Ser (c.1096C>T) is classified Likely benign in CSNK2A1 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-08-01). AlphaMissense: likely benign (0.061); Very rare (popmax 0.00994%, sas); Associated with Inborn genetic diseases.

What condition is associated with CSNK2A1 p.Pro366Ser (c.1096C>T)?

CSNK2A1 p.Pro366Ser (c.1096C>T) is associated with Inborn genetic diseases (ClinVar).

How common is CSNK2A1 p.Pro366Ser (c.1096C>T) in the general population?

CSNK2A1 p.Pro366Ser (c.1096C>T) is very rare (popmax 0.00994%, sas) (gnomAD).

What do computational predictors say about CSNK2A1 p.Pro366Ser (c.1096C>T)?

AlphaMissense predicts likely benign (score 0.061) — an in-silico prediction, not a clinical call.

CSNK2A1 p.Pro366Ser

c.1096C>T · VCV4235180

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.061 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00994%, sas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.061	likely benign
REVEL	0.067	moderately benign-leaning
SaProt	LLR -5.42	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 2.4, phastCons 1
Regional constraint	o/e 0.47	unconstrained · MANE · 3,505 bp · p 2.9e-08 · regional, not allelic
Overall
CADD	22.7	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 0.00994% South Asian · 9/90,584 alleles

Filtering AF 0.00516% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00377%

Overall 0.000869% 14/1,611,452 alleles · very rare exomes 14/1,459,122 · genomes 0/152,330 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.00994%	10,065
Remaining individualsnot grpmax-eligible	0.00641%	15,595
European (non-Finnish)	8.48e-05%	1,178,946

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: CSNK2A1
Protein: p.Pro366Ser
Coding: c.1096C>T
MANE Select: NM_177559
Type: single nucleotide variant
Location: chr20:484041 (GRCh38)
Gene constraint: LOEUF 0.274 · pLI 1.00 · ClinGen HI 1/3 (gnomAD)
Structure: AlphaFold pLDDT 90.78 · 316 PDB

Full CSNK2A1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

CSNK2A1 p.Arg312Trp Pathogenic/Likely pathogenic ★★ same condition
CSNK2A1 p.Arg47Gln Pathogenic/Likely pathogenic ★★ same condition
CSNK2A1 c.511-3C>T Uncertain significance ★★ same condition
CSNK2A1 p.Gly199Asp Uncertain significance ★★ ⚠ same condition
CSNK2A1 p.His18Tyr Uncertain significance ★★ ⚠ same condition
CSNK2A1 p.Ala387Thr Benign/Likely benign ★★ same condition
CSNK2A1 p.Arg47Pro Likely pathogenic ★ same condition
CSNK2A1 p.Leu128Ter 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/csnk2a1-p-pro366ser (accessed [today's date]).

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