Is CAMK2B p.Ala660Ser (c.1978G>T) pathogenic?

CAMK2B p.Ala660Ser (c.1978G>T) is classified Uncertain significance in CAMK2B (ClinVar, Single submitter, 1 submitter; last evaluated 2022-07-26). AlphaMissense: likely benign (0.2291); Absent from gnomAD v4.1.

How common is CAMK2B p.Ala660Ser (c.1978G>T) in the general population?

CAMK2B p.Ala660Ser (c.1978G>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about CAMK2B p.Ala660Ser (c.1978G>T)?

AlphaMissense predicts likely benign (score 0.2291) — an in-silico prediction, not a clinical call.

CAMK2B p.Ala660Ser

c.1978G>T · rs565318645 · VCV2064110

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2291 · ACMG-weighted

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 1,601,020)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.2291	likely benign
REVEL	0.129	moderately benign-leaning
SaProt	LLR -9.57	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 5.9	GERP 0.82, phastCons 1
Regional constraint	o/e 0.62	unconstrained · MANE · 821 bp · p 1.5e-07 · regional, not allelic
Overall
CADD	26.2	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

No allele count reported in gnomAD v4.1 (AN 1,601,020). This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: CAMK2B
Protein: p.Ala660Ser
Coding: c.1978G>T
MANE Select: NM_001220
dbSNP: rs565318645
Type: single nucleotide variant
Location: chr7:44220085 (GRCh38)
Gene constraint: LOEUF 0.45 · pLI 1.00 · ClinGen HI 1/3 (gnomAD)
Structure: AlphaFold pLDDT 72.35 · 4 PDB
Residue 660: a UniProt-annotated variant site (in mrd54)

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

Similar variants

CAMK2B p.Ala660= Likely benign ★★ same residue
CAMK2B p.Ala660Thr Likely benign ★★ ⚠ same residue
CAMK2B p.Ala660Val 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

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-ala660ser (accessed [today's date]).

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