Is CAMK2D p.Cys462Ser (c.1385G>C) pathogenic?

CAMK2D p.Cys462Ser (c.1385G>C) is classified Uncertain significance in CAMK2D (ClinVar, Single submitter, 1 submitter; last evaluated 2024-09-30). AlphaMissense: likely pathogenic (0.9265); Absent from gnomAD v4.1.

How common is CAMK2D p.Cys462Ser (c.1385G>C) in the general population?

CAMK2D p.Cys462Ser (c.1385G>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about CAMK2D p.Cys462Ser (c.1385G>C)?

AlphaMissense predicts likely pathogenic (score 0.9265) — an in-silico prediction, not a clinical call.

CAMK2D p.Cys462Ser

c.1385G>C · VCV3721770

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9265 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.9265	likely pathogenic
REVEL	0.492	indeterminate
SaProt	LLR -12.03	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 7.6	GERP 2.1, phastCons 1
Regional constraint	o/e 0.80	unconstrained · MANE · 58 kb · p 0.0013 · regional, not allelic
Overall
CADD	27.2	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.

⚠ Isoform check: AlphaMissense numbered on a different transcript (AM C428S vs ClinVar C462S) — verify the residue.

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: CAMK2D
Protein: p.Cys462Ser
Coding: c.1385G>C
MANE Select: NM_001321571
Type: single nucleotide variant
Location: chr4:113457485 (GRCh38)
Gene constraint: LOEUF 0.447 · pLI 0.97 (gnomAD)
Structure: AlphaFold pLDDT 84.10 · 9 PDB
Residue 462: a β-strand

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-cys462ser (accessed [today's date]).

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