ACTB p.Pro322fs
c.963_964dup · VCV4895126
Likely pathogenic
Single submitter
Classification
Likely pathogenic
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
Consequence
frameshift
predicted LoF
gnomAD v4.1
Rare
Conditions
1
ACTB-related disorder
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Consequence | frameshift | predicted loss-of-function in a LoF-intolerant gene |
|---|---|---|
| NMD | escapes | premature termination codon within the last 50 nt of the penultimate exon (5 of 6, 19 nt from its 3' end) — the truncated protein is likely expressed. PVS1 input, not an applied code |
| Splicing | ||
| SpliceAI | — | not assessed · substitutions only |
| Constraint at this position | ||
| Conservation | phyloP 9.8 | GERP 1.8, phastCons 1 |
| Region caveats | ||
| Repeat context | seg dup | · reads may not map uniquely · confidence, not pathogenicity |
Predicted loss-of-function is descriptive, not an applied PVS1 code.
Variant & gene context
- Gene
- ACTB
- Protein
- p.Pro322fs
- Coding
- c.963_964dup
- MANE Select
- NM_001101
- Type
- Duplication
- Location
- chr7:5528023 (GRCh38)
- Gene constraint
- LOEUF 0.193 · pLI 1.00 · ClinGen HI 0/3 (gnomAD)
- Structure
- AlphaFold pLDDT 95.31 · 93 PDB
Disease context
ACTB-related disorder
Similar variants
- ACTB p.Pro322Arg Likely pathogenic ★ same residue
- ACTB p.Pro322= Likely benign ★ same residue
- ACTB p.Tyr337Ter Likely pathogenic same condition
- ACTB p.Arg183Trp Pathogenic ★★ same condition
- ACTB p.Arg206Gly Likely pathogenic ★★ same condition
- ACTB p.His40Tyr Pathogenic/Likely pathogenic ★★ same condition
- ACTB p.Thr297fs Likely pathogenic ★★ same condition
- ACTB p.Val159Ala 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/actb-p-pro322fs (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown