Is CAMK2B p.Ala409Val (c.1226C>T) pathogenic?

CAMK2B p.Ala409Val (c.1226C>T) is classified Uncertain significance in CAMK2B (ClinVar, Single submitter, 1 submitter; last evaluated 2023-02-01). AlphaMissense: likely benign (0.0675); Very rare (popmax 0.00286%, eas).

How common is CAMK2B p.Ala409Val (c.1226C>T) in the general population?

CAMK2B p.Ala409Val (c.1226C>T) is very rare (popmax 0.00286%, eas) (gnomAD).

What do computational predictors say about CAMK2B p.Ala409Val (c.1226C>T)?

AlphaMissense predicts likely benign (score 0.0675) — an in-silico prediction, not a clinical call.

CAMK2B p.Ala409Val

c.1226C>T · rs2096557355 · VCV2126179

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0675 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00286%, eas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0675	likely benign
REVEL	0.121	moderately benign-leaning
SaProt	LLR -7.10	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 -0.43	GERP -3.6
Regional constraint	o/e 1.05	unconstrained · MANE · 19 kb · p 0.35 · regional, not allelic
Overall
CADD	12.6	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 0.00286% East Asian · 1/35,014 alleles

Filtering AF 3.1e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.2e-05%

Overall 0.000237% 3/1,267,930 alleles · very rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00286%	35,014
European (non-Finnish)	0.000185%	541,410

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: CAMK2B
Protein: p.Ala409Val
Coding: c.1226C>T
MANE Select: NM_001220
dbSNP: rs2096557355
Type: single nucleotide variant
Location: chr7:44229501 (GRCh38)
Gene constraint: LOEUF 0.45 · pLI 1.00 · ClinGen HI 1/3 (gnomAD)
Structure: AlphaFold pLDDT 72.35 · 4 PDB
Residue 409: a UniProt-annotated variant site (in mrd54); the 'disordered' region

Full CAMK2B gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CAMK2B p.Ala409Asp Uncertain significance ★★ ⚠ same residue
CAMK2B c.903+2T>C Likely pathogenic ★★ same type
CAMK2B p.Arg29Ter Pathogenic/Likely pathogenic ★★ same type
CAMK2B p.Glu110Lys Pathogenic ★★ same type
CAMK2B p.Glu237Lys Pathogenic ★★ same type
CAMK2B p.Lys301Glu Pathogenic/Likely pathogenic ★★ same type
CAMK2B p.Pro139Leu Pathogenic/Likely pathogenic ★★ same type
CAMK2B c.1059+1G>A Uncertain significance ★★ 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/camk2b-p-ala409val (accessed [today's date]).

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