NEK2 p.Phe148=
c.444C>T · rs543850404 · VCV1553373
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.0165%, sas)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Splicing | ||
| SpliceAI | <0.2 | no splice effect predicted · four deltas, not one · how we know |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP 2.1 | GERP 2.1, phastCons 1 |
| Overall | ||
| CADD | 9.818 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0165%
South Asian · 15/91,082 alleles
Filtering AF
0.0101%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00811%
Overall
0.00186%
30/1,614,110 alleles · ultra-rare
exomes 28/1,461,850 · genomes 2/152,260 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| South Asiangrpmax | 0.0165% | 6,072 |
| Remaining individualsnot grpmax-eligible | 0.0016% | 62,502 |
| European (non-Finnish) | 0.00119% | 84,286 |
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.Phe148=
- Coding
- c.444C>T
- MANE Select
- NM_002497
- dbSNP
- rs543850404
- Type
- single nucleotide variant
- Location
- chr1:211673594 (GRCh38)
- Gene constraint
- LOEUF 0.648 · pLI 0.04 (gnomAD)
- Structure
- AlphaFold pLDDT 78.52 · 30 PDB
- Residue 148
- the protein kinase domain; a β-strand
Similar variants
- 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
- NEK2 p.Arg318Ter 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-phe148 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown