Is PLK1 p.Val384Phe (c.1150G>T) pathogenic?

PLK1 p.Val384Phe (c.1150G>T) is classified Uncertain significance in PLK1 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-06-05). AlphaMissense: ambiguous (0.5129); Absent from gnomAD v4.1.

How common is PLK1 p.Val384Phe (c.1150G>T) in the general population?

PLK1 p.Val384Phe (c.1150G>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about PLK1 p.Val384Phe (c.1150G>T)?

AlphaMissense predicts ambiguous (score 0.5129) — an in-silico prediction, not a clinical call.

PLK1 p.Val384Phe

c.1150G>T · VCV3934529

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.5129 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/2 damaging

REVEL, SaProt · AlphaMissense no call

Computational evidence

Protein change
AlphaMissense	0.5129	ambiguous
REVEL	0.091	moderately benign-leaning
SaProt	LLR -8.38	tolerated
⇒ REVEL and SaProt both call this tolerated; AlphaMissense makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 9.9	GERP 0.7, phastCons 1
Regional constraint	o/e 0.85	unconstrained · MANE · 6,547 bp · p 0.047 · regional, not allelic
Overall
CADD	22.9	PHRED · no single calibrated threshold — expert panels disagree

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: PLK1
Protein: p.Val384Phe
Coding: c.1150G>T
MANE Select: NM_005030
Type: single nucleotide variant
Location: chr16:23687582 (GRCh38)
Gene constraint: LOEUF 0.205 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 85.11 · 85 PDB
Residue 384: an α-helix

Full PLK1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

PLK1 p.Ile327Thr Uncertain significance ★★ ⚠ same type
PLK1 p.Glu140= Benign ★★ same type
PLK1 p.Ala26Thr Uncertain significance ★ ⚠ same type
PLK1 p.Ala279Thr Uncertain significance ★ ⚠ same type
PLK1 p.Ala30Thr Uncertain significance ★ ⚠ same type
PLK1 p.Ala34Pro Uncertain significance ★ ⚠ same type
PLK1 p.Ala386Val Uncertain significance ★ ⚠ same type
PLK1 p.Ala4Ser 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/plk1-p-val384phe (accessed [today's date]).

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