Benign/Likely benign
Multiple submitters
Classification
Benign/Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 3 submitters
gnomAD v4.1
Rare
low-frequency (popmax 1.07%, afr)
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 1.1 | GERP -2.5, phastCons 0.035 |
| Overall | ||
| CADD | 8.219 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
1.07%
African / African-American · 782/72,802 alleles
Filtering AF
1.01%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.987%
Overall
0.0584%
888/1,521,274 alleles · low-frequency
exomes 417/1,369,174 · genomes 471/152,100 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 1.07% | 93 |
| Admixed American | 0.0592% | 1,688 |
| Middle Eastern | 0.0517% | 1,934 |
| Remaining individualsnot grpmax-eligible | 0.0438% | 2,281 |
| European (non-Finnish) | 0.00381% | 26,239 |
| South Asian | 0.00116% | 86,380 |
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.Pro965=
- Coding
- c.2895G>A
- MANE Select
- NM_014264
- dbSNP
- rs6820138
- Type
- single nucleotide variant
- Location
- chr4:127898523 (GRCh38)
- Gene constraint
- LOEUF 0.619 · pLI 0.18 (gnomAD)
- Structure
- AlphaFold pLDDT 66.31 · 19 PDB
Similar variants
- PLK4 p.Pro965Leu 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-pro965 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown