Is CAMK2B p.Pro236fs (c.707_708del) pathogenic?

CAMK2B p.Pro236fs (c.707708del) is classified Uncertain significance in CAMK2B (ClinVar, Single submitter, 1 submitter; last evaluated 2022-03-19). Very rare (popmax 8.48e-05%, nfe).

How common is CAMK2B p.Pro236fs (c.707_708del) in the general population?

CAMK2B p.Pro236fs (c.707_708del) is very rare (popmax 8.48e-05%, nfe) (gnomAD).

CAMK2B p.Pro236fs

c.707_708del · rs2128966671 · VCV1522319

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 8.48e-05%, nfe)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function in a LoF-intolerant gene
NMD	predicted	premature termination codon in exon 10 of 24
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 7.6	GERP 2.1, phastCons 1

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 8.48e-05% European (non-Finnish) · 1/1,179,774 alleles

Overall 6.84e-05% 1/1,461,456 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.Pro236fs
Coding: c.707_708del
MANE Select: NM_001220
dbSNP: rs2128966671
Type: Deletion
Location: chr7:44242329 (GRCh38)
Gene constraint: LOEUF 0.45 · pLI 1.00 · ClinGen HI 1/3 (gnomAD)
Structure: AlphaFold pLDDT 72.35 · 4 PDB
Residue 236: the protein kinase domain; a UniProt-annotated variant site (in mrd54); a turn

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

Similar variants

CAMK2B p.Pro437fs Uncertain significance ★★ same type
CAMK2B c.903+17del Likely benign ★★ same type
CAMK2B c.66-2del Likely pathogenic ★ same type
CAMK2B c.1132-20_1155del Uncertain significance ★ same type
CAMK2B c.340_341+14del Uncertain significance ★ same type
CAMK2B c.696+4_696+5del Uncertain significance ★ same type
CAMK2B p.Ala425fs Uncertain significance ★ same type
CAMK2B p.Arg9fs 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-pro236fs (accessed [today's date]).

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