Is PLK4 p.Leu36Phe (c.108G>T) pathogenic?

PLK4 p.Leu36Phe (c.108G>T) is classified Uncertain significance in PLK4 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-09-27). AlphaMissense: likely benign (0.2459); Absent from gnomAD v4.1.

How common is PLK4 p.Leu36Phe (c.108G>T) in the general population?

PLK4 p.Leu36Phe (c.108G>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about PLK4 p.Leu36Phe (c.108G>T)?

AlphaMissense predicts likely benign (score 0.2459) — an in-silico prediction, not a clinical call.

PLK4 p.Leu36Phe

c.108G>T · rs1734946623 · VCV1020155

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2459 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.2459	likely benign
REVEL	0.158	moderately benign-leaning
SaProt	LLR -7.77	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 6.5	GERP 1.4, phastCons 1
Regional constraint	o/e 0.74	unconstrained · MANE · 4,902 bp · p 1.5e-05 · regional, not allelic
Overall
CADD	25.5	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: PLK4
Protein: p.Leu36Phe
Coding: c.108G>T
MANE Select: NM_014264
dbSNP: rs1734946623
Type: single nucleotide variant
Location: chr4:127881908 (GRCh38)
Gene constraint: LOEUF 0.619 · pLI 0.18 (gnomAD)
Structure: AlphaFold pLDDT 66.31 · 19 PDB
Residue 36: the protein kinase domain

Full PLK4 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

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-leu36phe (accessed [today's date]).

Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown