DVL3 p.Pro554=
c.1662G>C · rs745582894 · VCV1124064
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.0167%, amr)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP -6.7 | GERP -3.1 |
| Overall | ||
| CADD | 0.401 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0167%
Admixed American · 10/59,980 alleles
Filtering AF
0.009%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00681%
Overall
0.00583%
94/1,613,326 alleles · ultra-rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Admixed Americangrpmax | 0.0167% | 5,998 |
| European (non-Finnish) | 0.00678% | 14,749 |
| Remaining individualsnot grpmax-eligible | 0.0064% | 15,615 |
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
- DVL3
- Protein
- p.Pro554=
- Coding
- c.1662G>C
- MANE Select
- NM_004423
- dbSNP
- rs745582894
- Type
- single nucleotide variant
- Location
- chr3:184170169 (GRCh38)
- Gene constraint
- LOEUF 0.536 · pLI 0.70 (gnomAD)
- Structure
- AlphaFold pLDDT 59.50 · 9 PDB
- Residue 554
- the 'disordered' region
Similar variants
- DVL3 c.1715-1G>A Pathogenic/Likely pathogenic ★★ same type
- DVL3 p.Ala359Thr Uncertain significance ★★ ⚠ same type
- DVL3 p.Ala565Val Uncertain significance ★★ ⚠ same type
- DVL3 p.Ala593Val Uncertain significance ★★ ⚠ same type
- DVL3 p.Ala629Thr Uncertain significance ★★ ⚠ same type
- DVL3 p.Arg145Gln Uncertain significance ★★ ⚠ same type
- DVL3 p.Arg157Gln Uncertain significance ★★ ⚠ same type
- DVL3 p.Arg166Trp 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/dvl3-p-pro554 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown