PLK4 p.Ser129=
c.387T>C · rs745677293 · VCV1608263
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
very rare (popmax 0.00407%, 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 -0.34 | GERP -0.68, phastCons 0.25 |
| Overall | ||
| CADD | 8.159 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00407%
European (non-Finnish) · 48/1,179,352 alleles
Filtering AF
0.00315%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00279%
Overall
0.00304%
49/1,613,212 alleles · very rare
exomes 47/1,461,042 · genomes 2/152,170 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| European (non-Finnish)grpmax | 0.00407% | 24,570 |
| Admixed American | 0.00167% | 59,976 |
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.Ser129=
- Coding
- c.387T>C
- MANE Select
- NM_014264
- dbSNP
- rs745677293
- Type
- single nucleotide variant
- Location
- chr4:127885757 (GRCh38)
- Gene constraint
- LOEUF 0.619 · pLI 0.18 (gnomAD)
- Structure
- AlphaFold pLDDT 66.31 · 19 PDB
- Residue 129
- the protein kinase domain; an α-helix
Similar variants
- 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
- PLK4 p.Arg371Gln 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-ser129 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown