Is CAMK2B p.Ala111Pro (c.331G>C) pathogenic?

CAMK2B p.Ala111Pro (c.331G>C) is classified Uncertain significance in CAMK2B (ClinVar, Single submitter, 1 submitter; last evaluated 2024-06-20). AlphaMissense: likely pathogenic (0.9828); Absent from gnomAD v4.1; Associated with intellectual developmental disorder, autosomal dominant 54.

What condition is associated with CAMK2B p.Ala111Pro (c.331G>C)?

CAMK2B p.Ala111Pro (c.331G>C) is associated with intellectual developmental disorder, autosomal dominant 54 (ClinVar).

How common is CAMK2B p.Ala111Pro (c.331G>C) in the general population?

CAMK2B p.Ala111Pro (c.331G>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about CAMK2B p.Ala111Pro (c.331G>C)?

AlphaMissense predicts likely pathogenic (score 0.9828) — an in-silico prediction, not a clinical call.

CAMK2B p.Ala111Pro

c.331G>C · rs2486549479 · VCV2444364

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9828 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

intellectual developmental disorder, autosomal dominant 54

Computational evidence

Protein change
AlphaMissense	0.9828	likely pathogenic
REVEL	0.437	indeterminate
SaProt	LLR -14.29	damaging
⇒ AlphaMissense and SaProt both call this damaging; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.5	GERP 1.9, phastCons 1
Regional constraint	o/e 0.28	constrained · MANE · 45 kb · p 1.2e-43 · regional, not allelic
Overall
CADD	29.0	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — 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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: CAMK2B
Protein: p.Ala111Pro
Coding: c.331G>C
MANE Select: NM_001220
dbSNP: rs2486549479
Type: single nucleotide variant
Location: chr7:44254552 (GRCh38)
Gene constraint: LOEUF 0.45 · pLI 1.00 · ClinGen HI 1/3 (gnomAD)
Structure: AlphaFold pLDDT 72.35 · 4 PDB
Residue 111: the protein kinase domain; a UniProt-annotated variant site (in mrd54); an α-helix

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

Disease context

intellectual developmental disorder, autosomal dominant 54 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

CAMK2B p.Arg29Ter Pathogenic/Likely pathogenic ★★ same condition
CAMK2B p.Glu110Lys Pathogenic ★★ same condition
CAMK2B p.Glu237Lys Pathogenic ★★ same condition
CAMK2B p.Lys301Glu Pathogenic/Likely pathogenic ★★ same condition
CAMK2B p.Pro139Leu Pathogenic/Likely pathogenic ★★ same condition
CAMK2B c.1597+1G>A Uncertain significance ★★ same condition
CAMK2B p.Glu547Gln Uncertain significance ★★ ⚠ same condition
CAMK2B p.Ile525Val 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-ala111pro (accessed [today's date]).

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