DACT1 p.Ser748=
c.2244C>T · rs758072910 · VCV722095
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
ultra-rare (popmax 0.0365%, nfe)
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 0.1 | GERP -0.9, phastCons 0.92 |
| Overall | ||
| CADD | 14.63 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0365%
European (non-Finnish) · 431/1,180,042 alleles
Filtering AF
0.0337%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0325%
Overall
0.0278%
449/1,614,056 alleles · ultra-rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| European (non-Finnish)grpmax | 0.0365% | 2,738 |
| Remaining individualsnot grpmax-eligible | 0.0288% | 3,471 |
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.Ser748=
- Coding
- c.2244C>T
- MANE Select
- NM_001079520
- dbSNP
- rs758072910
- Type
- single nucleotide variant
- Location
- chr14:58646978 (GRCh38)
- Gene constraint
- LOEUF 0.703 · pLI 0.17 (gnomAD)
- Structure
- AlphaFold pLDDT 50.95
- Residue 748
- a UniProt-annotated variant site (in tbs2; the mutant protein is stable and expressed)
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-ser748 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown