Is CAMKK2 p.Val151Ile (c.451G>A) pathogenic?

CAMKK2 p.Val151Ile (c.451G>A) is classified Uncertain significance in CAMKK2 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-10-05). AlphaMissense: likely benign (0.1466); Very rare (popmax 0.00921%, eas).

How common is CAMKK2 p.Val151Ile (c.451G>A) in the general population?

CAMKK2 p.Val151Ile (c.451G>A) is very rare (popmax 0.00921%, eas) (gnomAD).

What do computational predictors say about CAMKK2 p.Val151Ile (c.451G>A)?

AlphaMissense predicts likely benign (score 0.1466) — an in-silico prediction, not a clinical call.

CAMKK2 p.Val151Ile

c.451G>A · rs201742753 · VCV3136822

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1466 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00921%, eas)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.1466	likely benign
REVEL	0.294	indeterminate
SaProt	LLR -9.36	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.6	GERP 1.7, phastCons 1
Regional constraint	o/e 0.77	unconstrained · MANE · 26 kb · p 1.1e-08 · regional, not allelic
Overall
CADD	26.6	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 0.00921% East Asian · 4/43,418 alleles

Filtering AF 0.00305% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00185%

Overall 0.000588% 8/1,361,590 alleles · very rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00921%	10,854
European (non-Finnish)	0.000354%	282,722

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.Val151Ile
Coding: c.451G>A
MANE Select: NM_001270485
dbSNP: rs201742753
Type: single nucleotide variant
Location: chr12:121274076 (GRCh38)
Gene constraint: LOEUF 0.649 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 67.93 · 24 PDB

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-val151ile (accessed [today's date]).

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