DVL1 p.Pro586=
c.1758G>A · rs61757368 · VCV1436313
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
very rare (popmax 0.00764%, 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 -0.6 | GERP -3.3, phastCons 0.006 |
| Overall | ||
| CADD | 4.812 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00764%
Admixed American · 4/52,388 alleles
Filtering AF
0.00616%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00576%
Overall
0.00619%
96/1,551,318 alleles · very rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Admixed Americangrpmax | 0.00764% | 13,097 |
| European (non-Finnish) | 0.00751% | 13,308 |
| Finnishnot grpmax-eligible | 0.00414% | 24,126 |
| Remaining individualsnot grpmax-eligible | 0.00332% | 30,118 |
| South Asian | 0.0012% | 83,400 |
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
- DVL1
- Protein
- p.Pro586=
- Coding
- c.1758G>A
- MANE Select
- NM_001330311
- dbSNP
- rs61757368
- Type
- single nucleotide variant
- Location
- chr1:1336472 (GRCh38)
- Gene constraint
- LOEUF 1.046 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 60.70 · 3 PDB
- Residue 586
- the 'disordered' region
Similar variants
- DVL1 p.Pro586Arg Benign/Likely benign ★★ same residue
- DVL1 p.Pro586Leu Uncertain significance ★ ⚠ same residue
- DVL1 p.Ala125Val Uncertain significance ★★ ⚠ same type
- DVL1 p.Ala288Val Uncertain significance ★★ ⚠ same type
- DVL1 p.Ala361Thr Uncertain significance ★★ ⚠ same type
- DVL1 p.Ala368Val Uncertain significance ★★ ⚠ same type
- DVL1 p.Ala667Pro Uncertain significance ★★ ⚠ same type
- DVL1 p.Arg108Trp 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/dvl1-p-pro586 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown