Is CAMKK2 p.Arg580Gln (c.1739G>A) pathogenic?

CAMKK2 p.Arg580Gln (c.1739G>A) is classified Likely benign in CAMKK2 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-05-03). AlphaMissense: likely benign (0.0618); Very rare (popmax 0.00446%, eas).

How common is CAMKK2 p.Arg580Gln (c.1739G>A) in the general population?

CAMKK2 p.Arg580Gln (c.1739G>A) is very rare (popmax 0.00446%, eas) (gnomAD).

What do computational predictors say about CAMKK2 p.Arg580Gln (c.1739G>A)?

AlphaMissense predicts likely benign (score 0.0618) — an in-silico prediction, not a clinical call.

CAMKK2 p.Arg580Gln

c.1739G>A · rs1234530777 · VCV2542137

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0618 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00446%, eas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0618	likely benign
REVEL	0.104	moderately benign-leaning
SaProt	LLR -6.28	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 -2.3	GERP -3.2
Regional constraint	o/e 1.13	unconstrained · MANE · 4,489 bp · p 0.16 · regional, not allelic
Overall
CADD	0.347	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 0.00446% East Asian · 2/44,840 alleles

Filtering AF 0.000739% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000277%

Overall 0.000481% 7/1,455,228 alleles · very rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00446%	22,420
European (non-Finnish)	0.000424%	235,763

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.Arg580Gln
Coding: c.1739G>A
MANE Select: NM_001270485
dbSNP: rs1234530777
Type: single nucleotide variant
Location: chr12:121240727 (GRCh38)
Gene constraint: LOEUF 0.649 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 67.93 · 24 PDB
Residue 580: 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-arg580gln (accessed [today's date]).

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