Is CAMK2B p.Ala2Ser (c.4G>T) pathogenic?

CAMK2B p.Ala2Ser (c.4G>T) is classified Conflicting classifications of pathogenicity in CAMK2B (ClinVar, Conflicting submitters, 2 submitters; last evaluated 2025-03-25). AlphaMissense: likely benign (0.1641); Very rare (popmax 0.00165%, afr); Associated with Inborn genetic diseases.

What condition is associated with CAMK2B p.Ala2Ser (c.4G>T)?

CAMK2B p.Ala2Ser (c.4G>T) is associated with Inborn genetic diseases (ClinVar).

How common is CAMK2B p.Ala2Ser (c.4G>T) in the general population?

CAMK2B p.Ala2Ser (c.4G>T) is very rare (popmax 0.00165%, afr) (gnomAD).

What do computational predictors say about CAMK2B p.Ala2Ser (c.4G>T)?

AlphaMissense predicts likely benign (score 0.1641) — an in-silico prediction, not a clinical call.

CAMK2B p.Ala2Ser

c.4G>T · rs1488399289 · VCV2615949

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.1641 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00165%, afr)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.1641	likely benign
REVEL	0.061	moderately benign-leaning
SaProt	LLR -11.03	damaging
⇒ SaProt calls this damaging; AlphaMissense and REVEL do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 5.5	GERP 0.24, phastCons 1
Regional constraint	o/e 0.90	unconstrained · MANE · 41 kb · p 0.5 · regional, not allelic
Overall
CADD	23.9	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 0.00165% African / African-American · 1/60,612 alleles

Overall 0.000172% 2/1,165,150 alleles · very rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00165%	60,612
European (non-Finnish)	0.000108%	923,600

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.Ala2Ser
Coding: c.4G>T
MANE Select: NM_001220
dbSNP: rs1488399289
Type: single nucleotide variant
Location: chr7:44325418 (GRCh38)
Gene constraint: LOEUF 0.45 · pLI 1.00 · ClinGen HI 1/3 (gnomAD)
Structure: AlphaFold pLDDT 72.35 · 4 PDB

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.Ala2Thr Uncertain significance ★ ⚠ same residue
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

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-ala2ser (accessed [today's date]).

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