Is CAMK2B p.Pro354Ser (c.1060C>T) pathogenic?

CAMK2B p.Pro354Ser (c.1060C>T) is classified Benign/Likely benign in CAMK2B (ClinVar, Multiple submitters, 3 submitters; last evaluated 2025-11-27). AlphaMissense: likely benign (0.1998); Ultra-rare (popmax 0.0509%, mid); Associated with Inborn genetic diseases.

What condition is associated with CAMK2B p.Pro354Ser (c.1060C>T)?

CAMK2B p.Pro354Ser (c.1060C>T) is associated with Inborn genetic diseases (ClinVar).

How common is CAMK2B p.Pro354Ser (c.1060C>T) in the general population?

CAMK2B p.Pro354Ser (c.1060C>T) is ultra-rare (popmax 0.0509%, mid) (gnomAD).

What do computational predictors say about CAMK2B p.Pro354Ser (c.1060C>T)?

AlphaMissense predicts likely benign (score 0.1998) — an in-silico prediction, not a clinical call.

CAMK2B p.Pro354Ser

c.1060C>T · rs368239239 · VCV1656082

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

AlphaMissense

likely benign

0.1998 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0509%, mid)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.1998	likely benign
REVEL	0.198	benign-leaning
SaProt	LLR -7.27	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 8.4	GERP 0.82, phastCons 1
Regional constraint	o/e 1.05	unconstrained · MANE · 19 kb · p 0.35 · regional, not allelic
Overall
CADD	25.3	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

Grpmax group 0.0509% Middle Eastern · 3/5,892 alleles

Filtering AF 0.0198% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0162%

Overall 0.0084% 132/1,571,200 alleles · ultra-rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0509%	1,964
Admixed American	0.0317%	3,159
Remaining individualsnot grpmax-eligible	0.0132%	7,574
European (non-Finnish)	0.00861%	11,610
African / African-American	0.0041%	24,397
Finnishnot grpmax-eligible	0.00321%	31,119

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.Pro354Ser
Coding: c.1060C>T
MANE Select: NM_001220
dbSNP: rs368239239
Type: single nucleotide variant
Location: chr7:44234461 (GRCh38)
Gene constraint: LOEUF 0.45 · pLI 1.00 · ClinGen HI 1/3 (gnomAD)
Structure: AlphaFold pLDDT 72.35 · 4 PDB
Residue 354: a UniProt-annotated variant site (in mrd54); the 'disordered' region

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

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

CAMK2B p.Lys301Glu Pathogenic/Likely pathogenic ★★ same condition
CAMK2B p.Ala409Asp Uncertain significance ★★ ⚠ same condition
CAMK2B p.Ala425Asp Uncertain significance ★★ ⚠ same condition
CAMK2B p.Ala481Val Uncertain significance ★★ ⚠ same condition
CAMK2B p.Arg30Cys Uncertain significance ★★ ⚠ same condition
CAMK2B p.Arg534Trp Uncertain significance ★★ ⚠ same condition
CAMK2B p.Asp12Glu Uncertain significance ★★ ⚠ same condition
CAMK2B p.Asp647Asn Uncertain significance ★★ ⚠ same condition

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-pro354ser (accessed [today's date]).

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