Is CAMK2B p.Ala615Ser (c.1843G>T) pathogenic?

CAMK2B p.Ala615Ser (c.1843G>T) is classified Likely benign in CAMK2B (ClinVar, Single submitter, 1 submitter; last evaluated 2024-09-21). AlphaMissense: ambiguous (0.5303); Very rare (popmax 0.00195%, nfe).

How common is CAMK2B p.Ala615Ser (c.1843G>T) in the general population?

CAMK2B p.Ala615Ser (c.1843G>T) is very rare (popmax 0.00195%, nfe) (gnomAD).

What do computational predictors say about CAMK2B p.Ala615Ser (c.1843G>T)?

AlphaMissense predicts ambiguous (score 0.5303) — an in-silico prediction, not a clinical call.

CAMK2B p.Ala615Ser

c.1843G>T · rs757820225 · VCV1658546

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.5303 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00195%, nfe)

Computational evidence

Protein change
AlphaMissense	0.5303	ambiguous
REVEL	0.503	indeterminate
SaProt	LLR -13.11	damaging
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.6	GERP 2.1, phastCons 1
Regional constraint	o/e 0.62	unconstrained · MANE · 821 bp · p 1.5e-07 · regional, not allelic
Overall
CADD	27.6	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 0.00195% European (non-Finnish) · 23/1,180,030 alleles

Filtering AF 0.0013% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00108%

Overall 0.00155% 25/1,613,224 alleles · very rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00195%	51,306
Remaining individualsnot grpmax-eligible	0.0016%	62,474
African / African-American	0.00133%	74,928

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.Ala615Ser
Coding: c.1843G>T
MANE Select: NM_001220
dbSNP: rs757820225
Type: single nucleotide variant
Location: chr7:44220220 (GRCh38)
Gene constraint: LOEUF 0.45 · pLI 1.00 · ClinGen HI 1/3 (gnomAD)
Structure: AlphaFold pLDDT 72.35 · 4 PDB
Residue 615: a UniProt-annotated variant site (in mrd54); a β-strand

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

Similar variants

CAMK2B p.Ala615Thr Uncertain significance ★ ⚠ same residue
CAMK2B p.Ala615= 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

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-ala615ser (accessed [today's date]).

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