DACT1 p.Trp642Arg
c.1924T>C · rs200977826 · VCV734469
Computational evidence
| Protein change | ||
| AlphaMissense | 0.9937 | likely pathogenic · top 4% in DACT1 |
|---|---|---|
| REVEL | 0.296 | indeterminate |
| SaProt | LLR -3.03 | tolerated |
| ⇒ AlphaMissense calls this damaging; SaProt does not; REVEL makes no call. | ||
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
| Constraint at this position | ||
| Conservation | phyloP 3.9 | GERP 2.7, phastCons 1 |
| Regional constraint | o/e 1.10 | unconstrained · MANE · 8,733 bp · p 0.0021 · regional, not allelic |
| Overall | ||
| CADD | 23.7 | PHRED · no single calibrated threshold — expert panels disagree |
AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.
⚠ Isoform check: AlphaMissense numbered on a different transcript (AM W679R vs ClinVar W642R) — verify the residue.
Population frequency
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Finnishnot grpmax-eligible | 0.196% | 509 |
| Admixed Americangrpmax | 0.07% | 1,428 |
| European (non-Finnish) | 0.0539% | 1,857 |
| South Asian | 0.0439% | 2,275 |
| Remaining individualsnot grpmax-eligible | 0.0273% | 3,662 |
| African / African-American | 0.00134% | 74,764 |
Finnish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.
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
- DACT1
- Protein
- p.Trp642Arg
- Coding
- c.1924T>C
- MANE Select
- NM_001079520
- dbSNP
- rs200977826
- Type
- single nucleotide variant
- Location
- chr14:58646658 (GRCh38)
- Gene constraint
- LOEUF 0.703 · pLI 0.17 (gnomAD)
- Structure
- AlphaFold pLDDT 50.95
- Residue 642
- a UniProt-annotated variant site (in tbs2; the mutant protein is stable and expressed); the 'disordered' region
Similar variants
- DACT1 p.Glu451Asp Uncertain significance ★★ ⚠ same type
- DACT1 c.635-121T>C Likely benign ★★ same type
- DACT1 p.Ala427Val Benign ★★ same type
- DACT1 p.Ala500= Benign ★★ same type
- DACT1 p.Asp409Asn Benign ★★ same type
- DACT1 p.Glu257Lys Benign/Likely benign ★★ same type
- DACT1 p.Glu49= Likely benign ★★ same type
- DACT1 p.Gly660Ser Benign ★★ 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/dact1-p-trp642arg (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown