Is CAMK2B p.Ala558Val (c.1673C>T) pathogenic?

CAMK2B p.Ala558Val (c.1673C>T) is classified Likely benign in CAMK2B (ClinVar, Single submitter, 1 submitter; last evaluated 2024-11-11). AlphaMissense: ambiguous (0.363); Very rare (popmax 0.00235%, sas).

How common is CAMK2B p.Ala558Val (c.1673C>T) in the general population?

CAMK2B p.Ala558Val (c.1673C>T) is very rare (popmax 0.00235%, sas) (gnomAD).

What do computational predictors say about CAMK2B p.Ala558Val (c.1673C>T)?

AlphaMissense predicts ambiguous (score 0.363) — an in-silico prediction, not a clinical call.

CAMK2B p.Ala558Val

c.1673C>T · rs749755008 · VCV2889466

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.363 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00235%, sas)

Missense predictors

1/2 damaging

REVEL, SaProt · AlphaMissense no call

Computational evidence

Protein change
AlphaMissense	0.363	ambiguous
REVEL	0.199	benign-leaning
SaProt	LLR -10.57	damaging
⇒ SaProt calls this damaging; REVEL does not; AlphaMissense makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 9.8	GERP 2.1, phastCons 1
Regional constraint	o/e 0.62	unconstrained · MANE · 821 bp · p 1.5e-07 · regional, not allelic
Overall
CADD	34.0	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 0.00235% South Asian · 2/85,188 alleles

Filtering AF 0.00039% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000146%

Overall 0.000495% 7/1,413,414 alleles · very rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.00235%	42,594
Admixed American	0.00188%	53,166
Finnishnot grpmax-eligible	0.00165%	60,558
European (non-Finnish)	0.00026%	384,689

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.Ala558Val
Coding: c.1673C>T
MANE Select: NM_001220
dbSNP: rs749755008
Type: single nucleotide variant
Location: chr7:44220826 (GRCh38)
Gene constraint: LOEUF 0.45 · pLI 1.00 · ClinGen HI 1/3 (gnomAD)
Structure: AlphaFold pLDDT 72.35 · 4 PDB
Residue 558: a UniProt-annotated variant site (in mrd54); an α-helix

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

Similar variants

CAMK2B p.Ala558Ser Uncertain significance ★ ⚠ same residue
CAMK2B p.Ala558Thr 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
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-ala558val (accessed [today's date]).

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