WNK2 p.Ala808=
c.2424G>A · VCV3470022
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
low-frequency (popmax 1.65%, mid)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| REVEL | 0.017 | moderately benign-leaning |
|---|---|---|
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
| Constraint at this position | ||
| Conservation | phyloP -1.4 | GERP -3.8 |
| Overall | ||
| CADD | 1.959 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
1.65%
Middle Eastern · 100/6,052 alleles
Filtering AF
1.39%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 1.29%
Overall
0.691%
11,143/1,612,384 alleles · low-frequency
exomes 10,301/1,460,656 · genomes 842/151,728 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Middle Easterngrpmax | 1.65% | 61 |
| Admixed American | 0.819% | 122 |
| European (non-Finnish) | 0.798% | 125 |
| Remaining individualsnot grpmax-eligible | 0.762% | 131 |
| Ashkenazi Jewishnot grpmax-eligible | 0.7% | 143 |
| Finnishnot grpmax-eligible | 0.263% | 380 |
| South Asian | 0.21% | 477 |
| African / African-American | 0.136% | 733 |
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.Ala808=
- Coding
- c.2424G>A
- MANE Select
- NM_006648
- Type
- single nucleotide variant
- Location
- chr9:93258972 (GRCh38)
- Gene constraint
- LOEUF 0.508 · pLI 0.12 (gnomAD)
- Structure
- AlphaFold pLDDT 44.29 · 2 PDB
Similar variants
- WNK2 p.Ala808Glu Uncertain significance ★ ⚠ same residue
- WNK2 p.Ala808Thr 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.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-ala808 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown