ACTA1 p.Pro334fs
c.1001del · VCV4712795
Uncertain significance
Single submitter
Classification
Uncertain significance
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
Consequence
frameshift
predicted LoF
gnomAD v4.1
Rare
Conditions
1
congenital myopathy 2a, typical, autosomal dominant
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Consequence | frameshift | predicted loss-of-function |
|---|---|---|
| NMD | escapes | premature termination codon in the last exon (7 of 7) — the truncated protein is likely expressed. PVS1 input, not an applied code |
| Splicing | ||
| SpliceAI | — | not assessed · substitutions only |
| Constraint at this position | ||
| Conservation | phyloP -9.1 | GERP -5.2 |
Predicted loss-of-function is descriptive, not an applied PVS1 code.
Variant & gene context
- Gene
- ACTA1
- Protein
- p.Pro334fs
- Coding
- c.1001del
- MANE Select
- NM_001100
- Type
- Deletion
- Location
- chr1:229431632 (GRCh38)
- Gene constraint
- LOEUF 0.931 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 95.21 · 5 PDB
- Residue 334
- a UniProt-annotated variant site (in cmyo2c)
Disease context
congenital myopathy 2a, typical, autosomal dominant — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatmentsFor Congenital myopathy with excess of thin filaments (Orphanet):
- Inheritance
- Autosomal dominant
Similar variants
- ACTA1 p.Pro334Arg Pathogenic ★★★ same residue
- ACTA1 p.Pro334Leu Likely pathogenic ★★★ same residue
- ACTA1 p.Pro334Ser Pathogenic ★★★ same residue
- ACTA1 p.Pro334Ala Uncertain significance ★★ ⚠ same residue
- ACTA1 p.Asp181fs Pathogenic ★★★ same condition
- ACTA1 p.Ala146fs Pathogenic/Likely pathogenic ★★ same condition
- ACTA1 p.Phe92del Pathogenic/Likely pathogenic ★★ same condition
- ACTA1 p.Asn117fs Likely pathogenic ★ same condition
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-pro334fs (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown