NEK2 p.Pro269=
c.807T>C · rs1487136685 · VCV2013304
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.00329%, sas)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP 2.8 | GERP 2.1, phastCons 0.98 |
| Overall | ||
| CADD | 11.32 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00329%
South Asian · 3/91,086 alleles
Filtering AF
0.000875%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.000443%
Overall
0.000248%
4/1,614,168 alleles · very rare
exomes 4/1,461,820 · genomes 0/152,348 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| South Asiangrpmax | 0.00329% | 30,362 |
| Remaining individualsnot grpmax-eligible | 0.0016% | 62,510 |
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
- NEK2
- Protein
- p.Pro269=
- Coding
- c.807T>C
- MANE Select
- NM_002497
- dbSNP
- rs1487136685
- Type
- single nucleotide variant
- Location
- chr1:211669291 (GRCh38)
- Gene constraint
- LOEUF 0.648 · pLI 0.04 (gnomAD)
- Structure
- AlphaFold pLDDT 78.52 · 30 PDB
- Residue 269
- the protein kinase domain; the 'interaction with pcnt' region
Similar variants
- NEK2 p.Pro269Thr Uncertain significance ★ ⚠ same residue
- NEK2 c.97-2A>G Uncertain significance ★★ same type
- NEK2 p.Arg130Gln Uncertain significance ★★ same type
- NEK2 p.Arg130Gly Uncertain significance ★★ ⚠ same type
- NEK2 p.Arg140Gln Uncertain significance ★★ ⚠ same type
- NEK2 p.Arg239His Uncertain significance ★★ ⚠ same type
- NEK2 p.Arg239Ser Uncertain significance ★★ ⚠ same type
- NEK2 p.Arg318Gln 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/nek2-p-pro269 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown