Is CSNK2A2 p.Phe132Ser (c.395T>C) pathogenic?

CSNK2A2 p.Phe132Ser (c.395T>C) is classified Uncertain significance in CSNK2A2 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-08-13). AlphaMissense: likely benign (0.3049); Very rare (popmax 0.00837%, amr).

How common is CSNK2A2 p.Phe132Ser (c.395T>C) in the general population?

CSNK2A2 p.Phe132Ser (c.395T>C) is very rare (popmax 0.00837%, amr) (gnomAD).

What do computational predictors say about CSNK2A2 p.Phe132Ser (c.395T>C)?

AlphaMissense predicts likely benign (score 0.3049) — an in-silico prediction, not a clinical call.

CSNK2A2 p.Phe132Ser

c.395T>C · VCV4235185

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.3049 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00837%, amr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.3049	likely benign
REVEL	0.213	benign-leaning
SaProt	LLR -9.24	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 9.3	GERP 1.4, phastCons 1
Regional constraint	o/e 0.71	unconstrained · MANE · 22 kb · p 0.0045 · regional, not allelic
Overall
CADD	26.1	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00837% Admixed American · 5/59,754 alleles

Filtering AF 0.00324% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00207%

Overall 0.0013% 21/1,612,672 alleles · very rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00837%	11,951
Remaining individualsnot grpmax-eligible	0.0016%	62,440
European (non-Finnish)	0.00127%	78,636

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: CSNK2A2
Protein: p.Phe132Ser
Coding: c.395T>C
MANE Select: NM_001896
Type: single nucleotide variant
Location: chr16:58174485 (GRCh38)
Gene constraint: LOEUF 0.424 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 94.91 · 59 PDB
Residue 132: the protein kinase domain; an α-helix

Full CSNK2A2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CSNK2A2 p.Phe132Val Uncertain significance ★ ⚠ same residue
CSNK2A2 c.104+271G>A Benign ★★ same type
CSNK2A2 c.104+50C>T Benign ★★ same type
CSNK2A2 c.369+188A>G Benign ★★ same type
CSNK2A2 c.370-122A>G Benign ★★ same type
CSNK2A2 c.514-60T>C Benign ★★ same type
CSNK2A2 c.727-29T>G Benign ★★ same type
CSNK2A2 c.828-140C>A Benign ★★ 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/csnk2a2-p-phe132ser (accessed [today's date]).

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