PLK4 p.Ile40=
c.120C>A · rs1560690277 · VCV1575570
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.00062%, nfe)
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 -0.37, phastCons 1 |
| Overall | ||
| CADD | 11.86 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00062%
European (non-Finnish) · 7/1,129,352 alleles
Filtering AF
0.000258%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.000166%
Overall
0.000449%
7/1,558,440 alleles · very rare
exomes 6/1,406,276 · genomes 1/152,164 · joint denominator
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
- PLK4
- Protein
- p.Ile40=
- Coding
- c.120C>A
- MANE Select
- NM_014264
- dbSNP
- rs1560690277
- Type
- single nucleotide variant
- Location
- chr4:127881920 (GRCh38)
- Gene constraint
- LOEUF 0.619 · pLI 0.18 (gnomAD)
- Structure
- AlphaFold pLDDT 66.31 · 19 PDB
- Residue 40
- the protein kinase domain; a β-strand
Similar variants
- PLK4 p.Ile40Met Uncertain significance ★ ⚠ same residue
- PLK4 c.1358+1G>C Likely pathogenic ★★ same type
- PLK4 p.Arg185Ter Pathogenic/Likely pathogenic ★★ same type
- PLK4 c.126+5G>C Uncertain significance ★★ same type
- PLK4 c.1935+4A>T Uncertain significance ★★ same type
- PLK4 p.Arg185Gln Uncertain significance ★★ same type
- PLK4 p.Arg247His Uncertain significance ★★ ⚠ same type
- PLK4 p.Arg28Ser 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/plk4-p-ile40 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown