Is CAMK2B p.Leu482Phe (c.1444C>T) pathogenic?

CAMK2B p.Leu482Phe (c.1444C>T) is classified Uncertain significance in CAMK2B (ClinVar, Single submitter, 1 submitter; last evaluated 2026-01-05). AlphaMissense: likely benign (0.0569); Very rare (popmax 7.25e-05%).

How common is CAMK2B p.Leu482Phe (c.1444C>T) in the general population?

CAMK2B p.Leu482Phe (c.1444C>T) is very rare (popmax 7.25e-05%) (gnomAD).

What do computational predictors say about CAMK2B p.Leu482Phe (c.1444C>T)?

AlphaMissense predicts likely benign (score 0.0569) — an in-silico prediction, not a clinical call.

CAMK2B p.Leu482Phe

c.1444C>T · rs1368457756 · VCV1497706

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0569 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 7.25e-05%)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0569	likely benign
REVEL	0.057	moderately benign-leaning
SaProt	LLR -8.86	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 5.4	GERP 1.6, phastCons 1
Regional constraint	o/e 1.05	unconstrained · MANE · 19 kb · p 0.35 · regional, not allelic
Overall
CADD	18.78	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 7.25e-05%

Overall 7.25e-05% 1/1,380,224 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: CAMK2B
Protein: p.Leu482Phe
Coding: c.1444C>T
MANE Select: NM_001220
dbSNP: rs1368457756
Type: single nucleotide variant
Location: chr7:44228820 (GRCh38)
Gene constraint: LOEUF 0.45 · pLI 1.00 · ClinGen HI 1/3 (gnomAD)
Structure: AlphaFold pLDDT 72.35 · 4 PDB
Residue 482: 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.Leu482= Benign/Likely benign ★★ 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-leu482phe (accessed [today's date]).

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