WNT3A p.Pro258=
c.774G>A · VCV4709443
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.0165%, mid)
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 -2.7 | GERP -3.7 |
| Overall | ||
| CADD | 6.405 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0165%
Middle Eastern · 1/6,060 alleles
Filtering AF
0.00323%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00207%
Overall
0.00205%
33/1,613,058 alleles · ultra-rare
exomes 27/1,460,730 · genomes 6/152,328 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Middle Easterngrpmax | 0.0165% | 6,060 |
| Admixed American | 0.00833% | 12,002 |
| Remaining individualsnot grpmax-eligible | 0.0048% | 20,829 |
| Ashkenazi Jewishnot grpmax-eligible | 0.00338% | 29,592 |
| European (non-Finnish) | 0.00195% | 51,301 |
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
- WNT3A
- Protein
- p.Pro258=
- Coding
- c.774G>A
- MANE Select
- NM_033131
- Type
- single nucleotide variant
- Location
- chr1:228059180 (GRCh38)
- Gene constraint
- LOEUF 0.76 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 88.62 · 4 PDB
- Residue 258
- a β-strand
Similar variants
- WNT3A p.Ala318Pro Uncertain significance ★★ ⚠ same type
- WNT3A p.Arg141His Uncertain significance ★★ ⚠ same type
- WNT3A p.Arg141Pro Uncertain significance ★★ ⚠ same type
- WNT3A p.Arg322Gln Uncertain significance ★★ ⚠ same type
- WNT3A p.Arg324Trp Uncertain significance ★★ ⚠ same type
- WNT3A p.Arg82His Uncertain significance ★★ ⚠ same type
- WNT3A p.Glu160Lys Uncertain significance ★★ ⚠ same type
- WNT3A p.Glu68Lys 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/wnt3a-p-pro258 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown