ACTA1 p.Asp294Glu
c.882C>G · VCV3364063
Uncertain significance
Single submitter
Classification
Uncertain significance
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
AlphaMissense
likely pathogenic
0.8565 · ACMG-weighted
gnomAD v4.1
Absent
absent from gnomAD v4.1
Missense predictors
2/3 damaging
AlphaMissense, REVEL, SaProt
Computational evidence
| Protein change | ||
| AlphaMissense | 0.8565 | likely pathogenic |
|---|---|---|
| REVEL | 0.766 | pathogenic-leaning |
| SaProt | LLR -9.47 | tolerated |
| ⇒ AlphaMissense and REVEL call this damaging; SaProt does not. | ||
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
| Constraint at this position | ||
| Conservation | phyloP 3.5 | GERP -0.072, phastCons 1 |
| Regional constraint | o/e 0.33 | constrained · MANE · 1,613 bp · p 1.6e-54 · regional, not allelic |
| Overall | ||
| CADD | 23.3 | PHRED · no single calibrated threshold — expert panels disagree |
AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.
Population frequency
gnomAD v4.1 · exomes + genomes
Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.
Variant & gene context
- Gene
- ACTA1
- Protein
- p.Asp294Glu
- Coding
- c.882C>G
- MANE Select
- NM_001100
- Type
- single nucleotide variant
- Location
- chr1:229431829 (GRCh38)
- Gene constraint
- LOEUF 0.931 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 95.21 · 5 PDB
- Residue 294
- an α-helix; a UniProt-annotated variant site (in cmyo2c; results in decreased motility due to abnormal interactions between actin and tropomyosin with tropomyosin stabilized in the 'off' position; the mutant protein incorporates into actin filaments and does not result in increased actin aggregation or disruption of the sarcomere)
Similar variants
- ACTA1 p.Asp294Tyr Uncertain significance ★ ⚠ same residue
- ACTA1 p.Asp294= Likely benign ★ same residue
- ACTA1 p.Asp294Val Pathogenic same residue
- ACTA1 c.617-5C>A Likely pathogenic ★★★ same type
- ACTA1 c.990+1G>T Pathogenic ★★★ same type
- ACTA1 p.Asp13Asn Likely pathogenic ★★★ same type
- ACTA1 p.Asp290His Pathogenic ★★★ same type
- ACTA1 p.Asp58Asn Likely pathogenic ★★★ 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/acta1-p-asp294glu (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown