Is PLK4 p.Arg185Ter (c.553C>T) pathogenic?

PLK4 p.Arg185Ter (c.553C>T) is classified Pathogenic/Likely pathogenic in PLK4 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2024-09-14). Very rare (popmax 0.00167%, amr); Associated with PLK4-related disorder.

What condition is associated with PLK4 p.Arg185Ter (c.553C>T)?

PLK4 p.Arg185Ter (c.553C>T) is associated with PLK4-related disorder (ClinVar).

How common is PLK4 p.Arg185Ter (c.553C>T) in the general population?

PLK4 p.Arg185Ter (c.553C>T) is very rare (popmax 0.00167%, amr) (gnomAD).

PLK4 p.Arg185Ter

c.553C>T · rs968676193 · VCV2858483

Pathogenic/Likely pathogenic Multiple submitters

Classification

Pathogenic/Likely pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

Consequence

nonsense (stop-gain)

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.00167%, amr)

Conditions

PLK4-related disorder

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	nonsense (stop-gain)	predicted loss-of-function
NMD	predicted	premature termination codon in exon 5 of 16
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 4.9	GERP 1.1, phastCons 1
Overall
CADD	38.0	PHRED · no single calibrated threshold — expert panels disagree

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00167% Admixed American · 1/60,022 alleles

Filtering AF 0.000183% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00012%

Overall 0.000479% 7/1,461,764 alleles · very rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00167%	60,022
European (non-Finnish)	0.000509%	196,655

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.Arg185Ter
Coding: c.553C>T
MANE Select: NM_014264
dbSNP: rs968676193
Type: single nucleotide variant
Location: chr4:127885923 (GRCh38)
Gene constraint: LOEUF 0.619 · pLI 0.18 (gnomAD)
Structure: AlphaFold pLDDT 66.31 · 19 PDB
Residue 185: the protein kinase domain

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

Disease context

PLK4-related disorder

Similar variants

PLK4 p.Arg185Gln Uncertain significance ★★ same residue
PLK4 c.126+1G>A Likely pathogenic ★ same condition
PLK4 c.1831-2A>G Likely pathogenic ★ same condition
PLK4 p.Ser884Ter Likely pathogenic ★ same condition
PLK4 p.Pro651Ser Uncertain significance ★ ⚠ same condition
PLK4 c.2322+6T>C Likely benign same condition
PLK4 p.Lys572fs Likely pathogenic ★ same condition
PLK4 p.Trp898fs Likely pathogenic ★ same condition

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-arg185ter (accessed [today's date]).

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