Is PLK3 p.Arg51Pro (c.152G>C) pathogenic?

PLK3 p.Arg51Pro (c.152G>C) is classified Uncertain significance in PLK3 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-09-22). AlphaMissense: likely benign (0.1531); Very rare (popmax 0.000611%, nfe).

How common is PLK3 p.Arg51Pro (c.152G>C) in the general population?

PLK3 p.Arg51Pro (c.152G>C) is very rare (popmax 0.000611%, nfe) (gnomAD).

What do computational predictors say about PLK3 p.Arg51Pro (c.152G>C)?

AlphaMissense predicts likely benign (score 0.1531) — an in-silico prediction, not a clinical call.

PLK3 p.Arg51Pro

c.152G>C · VCV4569582

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1531 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000611%, nfe)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Computational evidence

Protein change
AlphaMissense	0.1531	likely benign
REVEL	0.344	indeterminate
SaProt	LLR -10.53	damaging
⇒ SaProt calls this damaging; AlphaMissense does not; REVEL is indeterminate.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 9.4	GERP 1.6, phastCons 1
Regional constraint	o/e 0.90	unconstrained · MANE · 5,211 bp · p 0.0042 · regional, not allelic
Overall
CADD	25.4	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

Grpmax group 0.000611% European (non-Finnish) · 7/1,146,486 alleles

Filtering AF 0.000254% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000163%

Overall 0.000584% 9/1,540,368 alleles · very rare exomes 9/1,388,132 · genomes 0/152,236 · joint denominator

Ancestry group	Frequency	1 in
Remaining individualsnot grpmax-eligible	0.00334%	29,917
European (non-Finnish)grpmax	0.000611%	163,784

Remaining individuals shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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: PLK3
Protein: p.Arg51Pro
Coding: c.152G>C
MANE Select: NM_004073
Type: single nucleotide variant
Location: chr1:44800615 (GRCh38)
Gene constraint: LOEUF 0.766 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 80.95 · 1 PDB

Full PLK3 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

PLK3 p.Gln383= Benign ★★ same type
PLK3 p.Ala293Ser Uncertain significance ★ ⚠ same type
PLK3 p.Ala293Thr Uncertain significance ★ ⚠ same type
PLK3 p.Ala415Gly Uncertain significance ★ ⚠ same type
PLK3 p.Ala448Val Uncertain significance ★ ⚠ same type
PLK3 p.Ala453Pro Uncertain significance ★ ⚠ same type
PLK3 p.Ala572Gly Uncertain significance ★ ⚠ same type
PLK3 p.Arg120Cys 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/plk3-p-arg51pro (accessed [today's date]).

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