Is CAMK2B p.Phe554Leu (c.1662T>G) pathogenic?

CAMK2B p.Phe554Leu (c.1662T>G) is classified Uncertain significance in CAMK2B (ClinVar, Single submitter, 1 submitter; last evaluated 2025-11-24). AlphaMissense: likely pathogenic (0.9898); Absent from gnomAD v4.1.

How common is CAMK2B p.Phe554Leu (c.1662T>G) in the general population?

CAMK2B p.Phe554Leu (c.1662T>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about CAMK2B p.Phe554Leu (c.1662T>G)?

AlphaMissense predicts likely pathogenic (score 0.9898) — an in-silico prediction, not a clinical call.

CAMK2B p.Phe554Leu

c.1662T>G · VCV4845485

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9898 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.9898	likely pathogenic
REVEL	0.281	benign-leaning
SaProt	LLR -11.70	damaging
⇒ AlphaMissense and SaProt call this damaging; REVEL does not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -0.32	GERP -4.3, phastCons 0.002
Regional constraint	o/e 0.62	unconstrained · MANE · 821 bp · p 1.5e-07 · regional, not allelic
Overall
CADD	22.2	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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: CAMK2B
Protein: p.Phe554Leu
Coding: c.1662T>G
MANE Select: NM_001220
Type: single nucleotide variant
Location: chr7:44220837 (GRCh38)
Gene constraint: LOEUF 0.45 · pLI 1.00 · ClinGen HI 1/3 (gnomAD)
Structure: AlphaFold pLDDT 72.35 · 4 PDB
Residue 554: a UniProt-annotated variant site (in mrd54); an α-helix

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

Similar variants

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
CAMK2B c.1597+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-phe554leu (accessed [today's date]).

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