Is WNK2 p.Arg2017= (c.6051G>T) pathogenic?

WNK2 p.Arg2017= (c.6051G>T) is classified Likely benign in WNK2 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-09-27). Very rare (popmax 0.000171%, nfe).

How common is WNK2 p.Arg2017= (c.6051G>T) in the general population?

WNK2 p.Arg2017= (c.6051G>T) is very rare (popmax 0.000171%, nfe) (gnomAD).

WNK2 p.Arg2017=

c.6051G>T · VCV4605196

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.000171%, nfe)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.046	moderately benign-leaning
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 2.7	GERP -3.4, phastCons 1
Overall
CADD	6.659	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.000171% European (non-Finnish) · 2/1,171,356 alleles

Filtering AF 2.8e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.1e-05%

Overall 0.000125% 2/1,601,528 alleles · very rare exomes 2/1,449,242 · genomes 0/152,286 · joint denominator

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: WNK2
Protein: p.Arg2017=
Coding: c.6051G>T
MANE Select: NM_006648
Type: single nucleotide variant
Location: chr9:93299197 (GRCh38)
Gene constraint: LOEUF 0.508 · pLI 0.12 (gnomAD)
Structure: AlphaFold pLDDT 44.29 · 2 PDB
Residue 2017: the 'disordered' region

Full WNK2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

WNK2 p.Arg2017Gln Uncertain significance ★ ⚠ same residue
WNK2 p.Arg2017Gly Uncertain significance ★ ⚠ same residue
WNK2 p.Arg2017Trp Uncertain significance ★ same residue
WNK2 p.Pro1819Leu Uncertain significance ★★ ⚠ same type
WNK2 c.2190+7G>A Benign ★★ same type
WNK2 p.Ala2109= Benign/Likely benign ★★ same type
WNK2 p.Ala808= Likely benign ★★ same type
WNK2 p.Arg1849Trp Likely benign ★★ 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/wnk2-p-arg2017 (accessed [today's date]).

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