Is NEK2 p.Arg73= (c.217C>A) pathogenic?

NEK2 p.Arg73= (c.217C>A) is classified Likely benign in NEK2 (ClinVar, Single submitter, 2 submitters; last evaluated 2022-07-06). Absent from gnomAD v4.1.

How common is NEK2 p.Arg73= (c.217C>A) in the general population?

NEK2 p.Arg73= (c.217C>A) is absent from gnomAD v4.1 (gnomAD).

NEK2 p.Arg73=

c.217C>A · rs145931962 · VCV1379810

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 2 submitters

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	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 3.6	GERP -2.7, phastCons 1
Overall
CADD	10.74	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.Arg73=
Coding: c.217C>A
MANE Select: NM_002497
dbSNP: rs145931962
Type: single nucleotide variant
Location: chr1:211674393 (GRCh38)
Gene constraint: LOEUF 0.648 · pLI 0.04 (gnomAD)
Structure: AlphaFold pLDDT 78.52 · 30 PDB
Residue 73: the protein kinase domain; a β-strand

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-arg73 (accessed [today's date]).

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