WNT4 p.Ser66=
c.198G>A · rs772566671 · VCV2062489
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.04%, amr)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| REVEL | 0.26 | benign-leaning |
|---|---|---|
| Splicing | ||
| SpliceAI | <0.2 | no splice effect predicted · four deltas, not one · how we know |
| Constraint at this position | ||
| Conservation | phyloP -20 | GERP -4.7 |
| Overall | ||
| CADD | 0.249 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.04%
Admixed American · 24/60,024 alleles
Filtering AF
0.0275%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0234%
Overall
0.00434%
70/1,614,028 alleles · ultra-rare
exomes 60/1,461,708 · genomes 10/152,320 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Admixed Americangrpmax | 0.04% | 2,501 |
| Middle Eastern | 0.0165% | 6,062 |
| Remaining individualsnot grpmax-eligible | 0.0128% | 7,813 |
| European (non-Finnish) | 0.00271% | 36,877 |
| African / African-American | 0.00266% | 37,531 |
| South Asian | 0.0022% | 45,542 |
| Finnishnot grpmax-eligible | 0.00157% | 63,854 |
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
- WNT4
- Protein
- p.Ser66=
- Coding
- c.198G>A
- MANE Select
- NM_030761
- dbSNP
- rs772566671
- Type
- single nucleotide variant
- Location
- chr1:22129731 (GRCh38)
- Gene constraint
- LOEUF 0.694 · pLI 0.05 (gnomAD)
- Structure
- AlphaFold pLDDT 91.41
Similar variants
- WNT4 p.Ser66Leu Uncertain significance ★ ⚠ same residue
- WNT4 p.Ala114Ser Uncertain significance ★★ ⚠ same type
- WNT4 p.Ala223Thr Uncertain significance ★★ ⚠ same type
- WNT4 p.Arg126Gln Uncertain significance ★★ ⚠ same type
- WNT4 p.Arg126Trp Uncertain significance ★★ ⚠ same type
- WNT4 p.Arg247Cys Uncertain significance ★★ same type
- WNT4 p.Arg285His Uncertain significance ★★ ⚠ same type
- WNT4 p.Arg294His 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/wnt4-p-ser66 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown