DVL1 p.Pro643=
c.1929G>A · rs770548436 · VCV2888472
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
very rare (popmax 0.00746%, 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 -12 | GERP -3.1 |
| Overall | ||
| CADD | 0.04 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00746%
Admixed American · 4/53,614 alleles
Filtering AF
0.00313%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0028%
Overall
0.00353%
55/1,557,078 alleles · very rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Admixed Americangrpmax | 0.00746% | 13,403 |
| European (non-Finnish) | 0.00406% | 24,648 |
| Remaining individualsnot grpmax-eligible | 0.00331% | 30,247 |
| South Asian | 0.00232% | 43,040 |
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.Pro643=
- Coding
- c.1929G>A
- MANE Select
- NM_001330311
- dbSNP
- rs770548436
- Type
- single nucleotide variant
- Location
- chr1:1336301 (GRCh38)
- Gene constraint
- LOEUF 1.046 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 60.70 · 3 PDB
- Residue 643
- the 'disordered' region
Similar variants
- DVL1 p.Pro643Leu 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
- 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-pro643 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown