Is CAMK2B p.Ala660Val (c.1979C>T) pathogenic?

CAMK2B p.Ala660Val (c.1979C>T) is classified Likely benign in CAMK2B (ClinVar, Multiple submitters, 2 submitters; last evaluated 2023-09-10). AlphaMissense: likely pathogenic (0.5671); Very rare (popmax 0.00349%, nfe).

How common is CAMK2B p.Ala660Val (c.1979C>T) in the general population?

CAMK2B p.Ala660Val (c.1979C>T) is very rare (popmax 0.00349%, nfe) (gnomAD).

What do computational predictors say about CAMK2B p.Ala660Val (c.1979C>T)?

AlphaMissense predicts likely pathogenic (score 0.5671) — an in-silico prediction, not a clinical call.

CAMK2B p.Ala660Val

c.1979C>T · rs778590827 · VCV1348342

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely pathogenic

0.5671 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00349%, nfe)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.5671	likely pathogenic
REVEL	0.346	indeterminate
SaProt	LLR -9.95	tolerated
⇒ AlphaMissense calls this damaging; SaProt does not; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 1.9, phastCons 1
Regional constraint	o/e 0.62	unconstrained · MANE · 821 bp · p 1.5e-07 · regional, not allelic
Overall
CADD	32.0	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 0.00349% European (non-Finnish) · 41/1,175,954 alleles

Filtering AF 0.00259% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00233%

Overall 0.00275% 44/1,600,106 alleles · very rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00349%	28,682
East Asian	0.00225%	44,382
Finnishnot grpmax-eligible	0.00173%	57,824
Remaining individualsnot grpmax-eligible	0.00161%	62,070

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.Ala660Val
Coding: c.1979C>T
MANE Select: NM_001220
dbSNP: rs778590827
Type: single nucleotide variant
Location: chr7:44220084 (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.Ala660Ser Uncertain significance ★ ⚠ 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-ala660val (accessed [today's date]).

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