ACTA2 c.454+1del
Pathogenic
Single submitter
Classification
Pathogenic
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
Consequence
canonical splice-site (±1/±2)
predicted LoF
gnomAD v4.1
Not reported
no gnomAD frequency available for this variant
Conditions
1
Descending aortic dissection
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Consequence | canonical splice-site (±1/±2) | predicted loss-of-function in a LoF-intolerant gene |
|---|---|---|
| Splicing | ||
| Splice region | donor +1 | canonical splice dinucleotide (donor +1) · inside the BP7-excluded zone |
| SpliceAI | — | not assessed · substitutions only |
| Constraint at this position | ||
| Conservation | phyloP 11 | GERP 2, phastCons 1 |
| Non-coding constraint | Z 3.67 | 1 kb window · o/e 0.75 · regional · uncalibrated |
Predicted loss-of-function is descriptive, not an applied PVS1 code.
Population frequency
dbSNP / gnomAD
No gnomAD frequency available for this variant. This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.
Variant & gene context
- Gene
- ACTA2
- Coding
- c.454+1del
- MANE Select
- NM_001613
- dbSNP
- rs2133256226
- Type
- Deletion
- Location
- chr10:88941784 (GRCh38)
- Gene constraint
- LOEUF 0.472 · pLI 0.99 · ClinGen HI 1/3 (gnomAD)
- Structure
- AlphaFold pLDDT 95.43
Similar variants
- ACTA2 c.130-2del Pathogenic/Likely pathogenic ★★ same type
- ACTA2 c.259-17del Likely benign ★★ same type
- ACTA2 c.991-1del Likely pathogenic ★ same type
- ACTA2 p.Met307fs Pathogenic ★ same type
- ACTA2 c.455-3del Conflicting classifications of pathogenicity ★ same type
- ACTA2 p.Cys219_Leu223del Uncertain significance ★ same type
- ACTA2 p.Cys376fs Uncertain significance ★ same type
- ACTA2 p.Glu102fs 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/acta2-c-454-plus-1del (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown