Is CAMK2G p.Pro440Ser (c.1318C>T) pathogenic?

CAMK2G p.Pro440Ser (c.1318C>T) is classified Uncertain significance in CAMK2G (ClinVar, Single submitter, 1 submitter; last evaluated 2022-02-03). AlphaMissense: likely benign (0.0653); Very rare (popmax 0.000349%, nfe).

How common is CAMK2G p.Pro440Ser (c.1318C>T) in the general population?

CAMK2G p.Pro440Ser (c.1318C>T) is very rare (popmax 0.000349%, nfe) (gnomAD).

What do computational predictors say about CAMK2G p.Pro440Ser (c.1318C>T)?

AlphaMissense predicts likely benign (score 0.0653) — an in-silico prediction, not a clinical call.

CAMK2G p.Pro440Ser

c.1318C>T · rs972847059 · VCV2206079

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0653 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000349%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0653	likely benign
REVEL	0.11	moderately benign-leaning
SaProt	LLR -5.50	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 1.6, phastCons 1
Regional constraint	o/e 0.76	unconstrained · MANE · 25 kb · p 3.8e-06 · regional, not allelic
Overall
CADD	25.2	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — 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 P410S vs ClinVar P440S) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.000349% European (non-Finnish) · 4/1,146,886 alleles

Filtering AF 8.2e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 5.5e-05%

Overall 0.000286% 4/1,396,940 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: CAMK2G
Protein: p.Pro440Ser
Coding: c.1318C>T
MANE Select: NM_001367534
dbSNP: rs972847059
Type: single nucleotide variant
Location: chr10:73819577 (GRCh38)
Gene constraint: LOEUF 0.404 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 79.50 · 2 PDB
Residue 440: an α-helix

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

Similar variants

CAMK2G p.Arg292Pro Pathogenic/Likely pathogenic ★★ same type
CAMK2G p.Arg553Trp Uncertain significance ★★ ⚠ same type
CAMK2G p.Asn394Ser Uncertain significance ★★ ⚠ same type
CAMK2G p.Ile261Thr Uncertain significance ★★ ⚠ same type
CAMK2G p.Thr383Met Uncertain significance ★★ ⚠ same type
CAMK2G p.Thr523Ser Uncertain significance ★★ ⚠ same type
CAMK2G p.Val89Met Uncertain significance ★★ ⚠ same type
CAMK2G c.161-110A>G Benign ★★ 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/camk2g-p-pro440ser (accessed [today's date]).

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