DACT1 p.Leu554=
c.1662C>G · rs1296666959 · VCV750271
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.000765%, 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 -3.7 | GERP -3.6 |
| Overall | ||
| CADD | 0.668 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.000765%
European (non-Finnish) · 9/1,177,234 alleles
Filtering AF
0.00036%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.000261%
Overall
0.000562%
9/1,602,768 alleles · very rare
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.Leu554=
- Coding
- c.1662C>G
- MANE Select
- NM_001079520
- dbSNP
- rs1296666959
- Type
- single nucleotide variant
- Location
- chr14:58646396 (GRCh38)
- Gene constraint
- LOEUF 0.703 · pLI 0.17 (gnomAD)
- Structure
- AlphaFold pLDDT 50.95
- Residue 554
- a UniProt-annotated variant site (in tbs2; the mutant protein is stable and expressed)
Similar variants
- DACT1 p.Leu554Phe Pathogenic ⚠ same residue
- 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
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-leu554 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown