Is NEK2 p.Arg280= (c.840A>G) pathogenic?

NEK2 p.Arg280= (c.840A>G) is classified Likely benign in NEK2 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-08-04). Absent from gnomAD v4.1.

How common is NEK2 p.Arg280= (c.840A>G) in the general population?

NEK2 p.Arg280= (c.840A>G) is absent from gnomAD v4.1 (gnomAD).

NEK2 p.Arg280=

c.840A>G · rs2464388328 · VCV2836699

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Absent

absent from gnomAD v4.1

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · T>A here scores Δ0.23 · evaluated, not missing
Constraint at this position
Conservation	phyloP -0.38	GERP -4.1, phastCons 0.001
Overall
CADD	6.911	PHRED · no single calibrated threshold — expert panels disagree

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: NEK2
Protein: p.Arg280=
Coding: c.840A>G
MANE Select: NM_002497
dbSNP: rs2464388328
Type: single nucleotide variant
Location: chr1:211669258 (GRCh38)
Gene constraint: LOEUF 0.648 · pLI 0.04 (gnomAD)
Structure: AlphaFold pLDDT 78.52 · 30 PDB
Residue 280: the 'interaction with pcnt' region

Full NEK2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

NEK2 c.97-2A>G Uncertain significance ★★ same type
NEK2 p.Arg130Gln Uncertain significance ★★ same type
NEK2 p.Arg130Gly Uncertain significance ★★ ⚠ same type
NEK2 p.Arg140Gln Uncertain significance ★★ ⚠ same type
NEK2 p.Arg239His Uncertain significance ★★ ⚠ same type
NEK2 p.Arg239Ser Uncertain significance ★★ ⚠ same type
NEK2 p.Arg318Gln Uncertain significance ★★ ⚠ same type
NEK2 p.Arg318Ter 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/nek2-p-arg280 (accessed [today's date]).

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