Is CAMK2D p.Val278Ile (c.832G>A) pathogenic?

CAMK2D p.Val278Ile (c.832G>A) is classified Uncertain significance in CAMK2D (ClinVar, Single submitter, 1 submitter; last evaluated 2026-02-25). AlphaMissense: likely benign (0.3041); Very rare (popmax 8.78e-05%, nfe).

How common is CAMK2D p.Val278Ile (c.832G>A) in the general population?

CAMK2D p.Val278Ile (c.832G>A) is very rare (popmax 8.78e-05%, nfe) (gnomAD).

What do computational predictors say about CAMK2D p.Val278Ile (c.832G>A)?

AlphaMissense predicts likely benign (score 0.3041) — an in-silico prediction, not a clinical call.

CAMK2D p.Val278Ile

c.832G>A · VCV4840458

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.3041 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 8.78e-05%, nfe)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.3041	likely benign
REVEL	0.223	benign-leaning
SaProt	LLR -10.88	damaging
⇒ SaProt calls this damaging; AlphaMissense and REVEL do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.6	GERP 2.1, phastCons 1
Regional constraint	o/e 0.39	unconstrained · MANE · 24 kb · p 8.9e-16 · regional, not allelic
Overall
CADD	25.1	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 8.78e-05% European (non-Finnish) · 1/1,138,518 alleles

Overall 0.000657% 1/152,164 alleles · very rare

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: CAMK2D
Protein: p.Val278Ile
Coding: c.832G>A
MANE Select: NM_001321571
Type: single nucleotide variant
Location: chr4:113513901 (GRCh38)
Gene constraint: LOEUF 0.447 · pLI 0.97 (gnomAD)
Structure: AlphaFold pLDDT 84.10 · 9 PDB
Residue 278: an α-helix

Full CAMK2D gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CAMK2D c.602-5T>C Benign ★★ same type
CAMK2D p.Asp167Glu Benign/Likely benign ★★ same type
CAMK2D p.Thr240= Benign/Likely benign ★★ same type
CAMK2D p.Arg275His Pathogenic ★ same type
CAMK2D p.Glu110Lys Likely pathogenic ★ same type
CAMK2D p.Gly210Arg Pathogenic ★ same type
CAMK2D p.Leu291Phe Pathogenic ★ same type
CAMK2D p.Phe294Ser 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/camk2d-p-val278ile (accessed [today's date]).

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