NEK2 p.Val35=
c.105T>C · rs569591376 · VCV1555822
Benign/Likely benign
Multiple submitters
Classification
Benign/Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
rare (popmax 0.137%, 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 0.66 | GERP -3.5, phastCons 0.96 |
| Overall | ||
| CADD | 8.469 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.137%
South Asian · 124/90,298 alleles
Filtering AF
0.118%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.11%
Overall
0.00903%
145/1,606,134 alleles · rare
exomes 140/1,453,798 · genomes 5/152,336 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| South Asiangrpmax | 0.137% | 728 |
| Remaining individualsnot grpmax-eligible | 0.0273% | 3,657 |
| East Asian | 0.00671% | 14,903 |
| Admixed American | 0.00169% | 59,252 |
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.Val35=
- Coding
- c.105T>C
- MANE Select
- NM_002497
- dbSNP
- rs569591376
- Type
- single nucleotide variant
- Location
- chr1:211674505 (GRCh38)
- Gene constraint
- LOEUF 0.648 · pLI 0.04 (gnomAD)
- Structure
- AlphaFold pLDDT 78.52 · 30 PDB
- Residue 35
- the protein kinase domain; a β-strand
Similar variants
- NEK2 p.Val35Ile 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-val35 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown