Is CAMKK2 p.Arg142Gln (c.425G>A) pathogenic?

CAMKK2 p.Arg142Gln (c.425G>A) is classified Uncertain significance in CAMKK2 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-08-27). AlphaMissense: ambiguous (0.4234); Ultra-rare (popmax 0.0189%, amr).

How common is CAMKK2 p.Arg142Gln (c.425G>A) in the general population?

CAMKK2 p.Arg142Gln (c.425G>A) is ultra-rare (popmax 0.0189%, amr) (gnomAD).

What do computational predictors say about CAMKK2 p.Arg142Gln (c.425G>A)?

AlphaMissense predicts ambiguous (score 0.4234) — an in-silico prediction, not a clinical call.

CAMKK2 p.Arg142Gln

c.425G>A · VCV4218469

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.4234 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0189%, amr)

Computational evidence

Protein change
AlphaMissense	0.4234	ambiguous
REVEL	0.371	indeterminate
SaProt	LLR -12.36	damaging
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 5.8	GERP 1.7, phastCons 1
Regional constraint	o/e 0.77	unconstrained · MANE · 26 kb · p 1.1e-08 · regional, not allelic
Overall
CADD	28.6	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 0.0189% Admixed American · 9/47,594 alleles

Filtering AF 0.00986% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00731%

Overall 0.00124% 19/1,536,046 alleles · ultra-rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.0189%	5,288
Remaining individualsnot grpmax-eligible	0.00508%	19,670
European (non-Finnish)	0.000613%	163,070

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: CAMKK2
Protein: p.Arg142Gln
Coding: c.425G>A
MANE Select: NM_001270485
Type: single nucleotide variant
Location: chr12:121274102 (GRCh38)
Gene constraint: LOEUF 0.649 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 67.93 · 24 PDB
Residue 142: the 'disordered' region

Full CAMKK2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CAMKK2 c.1235+3G>A Benign ★★ same type
CAMKK2 p.Asn118= Benign ★★ same type
CAMKK2 p.Gly22= Benign ★★ same type
CAMKK2 p.His150= Benign ★★ same type
CAMKK2 p.Ile297= Benign ★★ same type
CAMKK2 p.Pro351= Benign ★★ same type
CAMKK2 p.Ser133= Benign ★★ same type
CAMKK2 p.Ala15Val 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/camkk2-p-arg142gln (accessed [today's date]).

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