Is CAMK2G p.Cys290Arg (c.868T>C) pathogenic?

CAMK2G p.Cys290Arg (c.868T>C) is classified Uncertain significance in CAMK2G (ClinVar, Single submitter, 1 submitter; last evaluated 2022-05-22). AlphaMissense: likely pathogenic (0.9984); Absent from gnomAD v4.1; Associated with intellectual developmental disorder 59.

What condition is associated with CAMK2G p.Cys290Arg (c.868T>C)?

CAMK2G p.Cys290Arg (c.868T>C) is associated with intellectual developmental disorder 59 (ClinVar).

How common is CAMK2G p.Cys290Arg (c.868T>C) in the general population?

CAMK2G p.Cys290Arg (c.868T>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about CAMK2G p.Cys290Arg (c.868T>C)?

AlphaMissense predicts likely pathogenic (score 0.9984) — an in-silico prediction, not a clinical call.

CAMK2G p.Cys290Arg

c.868T>C · rs2134435974 · VCV1687265

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9984 · 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 59

Computational evidence

Protein change
AlphaMissense	0.9984	likely pathogenic
REVEL	0.59	indeterminate
SaProt	LLR -14.08	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 11	GERP 2.4, phastCons 1
Regional constraint	o/e 0.43	unconstrained · MANE · 33 kb · p 1.5e-29 · regional, not allelic
Overall
CADD	31.0	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: CAMK2G
Protein: p.Cys290Arg
Coding: c.868T>C
MANE Select: NM_001367534
dbSNP: rs2134435974
Type: single nucleotide variant
Location: chr10:73842493 (GRCh38)
Gene constraint: LOEUF 0.404 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 79.50 · 2 PDB
Residue 290: the 'autoinhibitory domain' region; an α-helix

Full CAMK2G gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

intellectual developmental disorder 59 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

CAMK2G p.Arg292Pro Pathogenic/Likely pathogenic ★★ same condition
CAMK2G p.Arg553Trp Uncertain significance ★★ ⚠ same condition
CAMK2G p.Ile261Thr Uncertain significance ★★ ⚠ same condition
CAMK2G p.Thr523Ser Uncertain significance ★★ ⚠ same condition
CAMK2G c.161-110A>G Benign ★★ same condition
CAMK2G c.275+69A>G Benign ★★ same condition
CAMK2G p.Lys49= Benign ★★ same condition
CAMK2G p.Asp412Glu Likely pathogenic ★ ⚠ 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/camk2g-p-cys290arg (accessed [today's date]).

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