DVL1 p.Pro646=
c.1938C>T · rs758190734 · VCV2193743
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
very rare (popmax 0.00555%, 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 -0.54 | GERP -3.1 |
| Overall | ||
| CADD | 0.647 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00555%
Admixed American · 3/54,052 alleles
Filtering AF
0.00156%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00132%
Overall
0.00211%
33/1,562,532 alleles · very rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Admixed Americangrpmax | 0.00555% | 18,017 |
| Remaining individualsnot grpmax-eligible | 0.00494% | 20,254 |
| European (non-Finnish) | 0.00224% | 44,642 |
| African / African-American | 0.00134% | 74,408 |
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.Pro646=
- Coding
- c.1938C>T
- MANE Select
- NM_001330311
- dbSNP
- rs758190734
- Type
- single nucleotide variant
- Location
- chr1:1336292 (GRCh38)
- Gene constraint
- LOEUF 1.046 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 60.70 · 3 PDB
- Residue 646
- the 'disordered' region
Similar variants
- DVL1 p.Pro646Leu Likely benign ★★ 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
- DVL1 p.Arg116Gln 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-pro646 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown