Is PLK4 p.Arg267Ter (c.799C>T) pathogenic?

PLK4 p.Arg267Ter (c.799C>T) is classified Pathogenic in PLK4 (ClinVar, Single submitter, 1 submitter; last evaluated 2021-07-14). Very rare (popmax 8.48e-05%, nfe).

How common is PLK4 p.Arg267Ter (c.799C>T) in the general population?

PLK4 p.Arg267Ter (c.799C>T) is very rare (popmax 8.48e-05%, nfe) (gnomAD).

PLK4 p.Arg267Ter

c.799C>T · rs1472376292 · VCV1952871

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

nonsense (stop-gain)

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 8.48e-05%, nfe)

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 3.3	GERP 0.24, phastCons 0.6
Overall
CADD	36.0	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 8.48e-05% European (non-Finnish) · 1/1,179,926 alleles

Overall 6.84e-05% 1/1,461,676 alleles · very rare

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.Arg267Ter
Coding: c.799C>T
MANE Select: NM_014264
dbSNP: rs1472376292
Type: single nucleotide variant
Location: chr4:127886169 (GRCh38)
Gene constraint: LOEUF 0.619 · pLI 0.18 (gnomAD)
Structure: AlphaFold pLDDT 66.31 · 19 PDB

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

Similar variants

PLK4 p.Arg267Gln Uncertain significance ★ ⚠ same residue
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

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-arg267ter (accessed [today's date]).

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