PLK4 p.Val54=
c.162A>G · rs199771668 · VCV436339
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 4 submitters
gnomAD v4.1
Rare
rare (popmax 0.382%, mid)
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 0.24 | GERP -2.2, phastCons 0.51 |
| Overall | ||
| CADD | 9.633 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.382%
Middle Eastern · 23/6,014 alleles
Filtering AF
0.261%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.222%
Overall
0.0092%
147/1,598,172 alleles · rare
exomes 132/1,445,792 · genomes 15/152,380 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Middle Easterngrpmax | 0.382% | 261 |
| Remaining individualsnot grpmax-eligible | 0.0291% | 3,441 |
| African / African-American | 0.0281% | 3,559 |
| South Asian | 0.0232% | 4,314 |
| Admixed American | 0.0167% | 5,993 |
| European (non-Finnish) | 0.00463% | 21,588 |
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.Val54=
- Coding
- c.162A>G
- MANE Select
- NM_014264
- dbSNP
- rs199771668
- Type
- single nucleotide variant
- Location
- chr4:127883297 (GRCh38)
- Gene constraint
- LOEUF 0.619 · pLI 0.18 (gnomAD)
- Structure
- AlphaFold pLDDT 66.31 · 19 PDB
- Residue 54
- the protein kinase domain; an α-helix
Similar variants
- PLK4 p.Val54Ile 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-val54 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown