WNK2 p.Pro976=
c.2928T>A · VCV3816568
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
ultra-rare (popmax 0.0577%, afr)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| REVEL | 0.08 | moderately benign-leaning |
|---|---|---|
| Splicing | ||
| SpliceAI | <0.2 | no splice effect predicted · four deltas, not one · how we know |
| Constraint at this position | ||
| Conservation | phyloP -0.11 | GERP -1.9, phastCons 0.006 |
| Overall | ||
| CADD | 2.655 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0577%
African / African-American · 11/19,080 alleles
Filtering AF
0.0323%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.025%
Overall
0.00436%
33/756,286 alleles · ultra-rare
exomes 27/718,764 · genomes 6/37,522 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 0.0577% | 1,735 |
| Finnishnot grpmax-eligible | 0.00956% | 10,455 |
| Admixed American | 0.00656% | 15,235 |
| Remaining individualsnot grpmax-eligible | 0.00354% | 28,238 |
| European (non-Finnish) | 0.00301% | 33,183 |
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.Pro976=
- Coding
- c.2928T>A
- MANE Select
- NM_006648
- Type
- single nucleotide variant
- Location
- chr9:93259476 (GRCh38)
- Gene constraint
- LOEUF 0.508 · pLI 0.12 (gnomAD)
- Structure
- AlphaFold pLDDT 44.29 · 2 PDB
- Residue 976
- the 'disordered' region
Similar variants
- WNK2 p.Pro976Arg 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
- WNK2 p.Gly908Ala Benign ★★ same type
- WNK2 p.His758Asn 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-pro976 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown