Is CAMK1 p.Pro345Ala (c.1033C>G) pathogenic?

CAMK1 p.Pro345Ala (c.1033C>G) is classified Uncertain significance in CAMK1 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-08-11). AlphaMissense: likely benign (0.0523); Very rare (popmax 0.00542%, nfe).

How common is CAMK1 p.Pro345Ala (c.1033C>G) in the general population?

CAMK1 p.Pro345Ala (c.1033C>G) is very rare (popmax 0.00542%, nfe) (gnomAD).

What do computational predictors say about CAMK1 p.Pro345Ala (c.1033C>G)?

AlphaMissense predicts likely benign (score 0.0523) — an in-silico prediction, not a clinical call.

CAMK1 p.Pro345Ala

c.1033C>G · VCV4218395

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0523 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00542%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0523	likely benign
REVEL	0.19	benign-leaning
SaProt	LLR -5.70	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 1.1	GERP 0.64, phastCons 0.43
Regional constraint	o/e 0.97	unconstrained · MANE · 10 kb · p 0.48 · regional, not allelic
Overall
CADD	1.035	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.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00542% European (non-Finnish) · 64/1,180,038 alleles

Filtering AF 0.00435% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00396%

Overall 0.00403% 65/1,614,074 alleles · very rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00542%	18,438
African / African-American	0.00133%	74,932

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: CAMK1
Protein: p.Pro345Ala
Coding: c.1033C>G
MANE Select: NM_003656
Type: single nucleotide variant
Location: chr3:9757619 (GRCh38)
Gene constraint: LOEUF 0.973 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 79.87 · 4 PDB

Full CAMK1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CAMK1 p.Pro345Leu Uncertain significance ★ ⚠ same residue
CAMK1 p.Pro345= Likely benign ★ same residue
CAMK1 p.Ser32Leu Uncertain significance ★★ ⚠ same type
CAMK1 p.Ala186Val Uncertain significance ★ ⚠ same type
CAMK1 p.Ala342Ser Uncertain significance ★ ⚠ same type
CAMK1 p.Ala47Thr Uncertain significance ★ ⚠ same type
CAMK1 p.Arg116Gln Uncertain significance ★ ⚠ same type
CAMK1 p.Arg116Trp Uncertain significance ★ ⚠ 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/camk1-p-pro345ala (accessed [today's date]).

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