Is PLK3 p.Ala293Ser (c.877G>T) pathogenic?

PLK3 p.Ala293Ser (c.877G>T) is classified Uncertain significance in PLK3 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-05-04). AlphaMissense: likely benign (0.074); Ultra-rare (popmax 0.0277%, nfe).

How common is PLK3 p.Ala293Ser (c.877G>T) in the general population?

PLK3 p.Ala293Ser (c.877G>T) is ultra-rare (popmax 0.0277%, nfe) (gnomAD).

What do computational predictors say about PLK3 p.Ala293Ser (c.877G>T)?

AlphaMissense predicts likely benign (score 0.074) — an in-silico prediction, not a clinical call.

PLK3 p.Ala293Ser

c.877G>T · rs200670234 · VCV2552678

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.074 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0277%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.074	likely benign
REVEL	0.033	moderately benign-leaning
SaProt	LLR -6.14	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.013	GERP 0.73
Regional constraint	o/e 0.90	unconstrained · MANE · 5,211 bp · p 0.0042 · regional, not allelic
Overall
CADD	1.561	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

Grpmax group 0.0277% European (non-Finnish) · 327/1,179,984 alleles

Filtering AF 0.0252% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0242%

Overall 0.0209% 338/1,613,674 alleles · ultra-rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.0277%	3,609
Remaining individualsnot grpmax-eligible	0.0128%	7,810
African / African-American	0.00401%	24,957

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.Ala293Ser
Coding: c.877G>T
MANE Select: NM_004073
dbSNP: rs200670234
Type: single nucleotide variant
Location: chr1:44803082 (GRCh38)
Gene constraint: LOEUF 0.766 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 80.95 · 1 PDB
Residue 293: the protein kinase domain; an α-helix

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

Similar variants

PLK3 p.Ala293Thr Uncertain significance ★ ⚠ same residue
PLK3 p.Gln383= Benign ★★ 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
PLK3 p.Arg154Gln 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-ala293ser (accessed [today's date]).

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