RELA p.Ala345fs
c.1034del · VCV4912311
Likely pathogenic
Single submitter
Classification
Likely pathogenic
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
Consequence
frameshift
predicted LoF
gnomAD v4.1
Rare
Conditions
1
RELA-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 in the last exon (11 of 11) — the truncated protein is likely expressed. PVS1 input, not an applied code |
| Splicing | ||
| SpliceAI | — | not assessed · substitutions only |
| Constraint at this position | ||
| Conservation | phyloP 0.26 | GERP -3.7, phastCons 0.84 |
Predicted loss-of-function is descriptive, not an applied PVS1 code.
Variant & gene context
- Gene
- RELA
- Protein
- p.Ala345fs
- Coding
- c.1034del
- MANE Select
- NM_021975
- Type
- Deletion
- Location
- chr11:65655000 (GRCh38)
- Gene constraint
- LOEUF 0.4 · pLI 1.00 (gnomAD)
- Structure
- AlphaFold pLDDT 73.52 · 88 PDB
- Residue 345
- the 'disordered' region; the 'transcriptional activation domain 3' region; a UniProt-annotated variant site (found in a patient diagnosed with autoimmune lymphoproliferative syndrome; uncertain significance)
Disease context
RELA-related disorder
Similar variants
- RELA p.Ala345= Likely benign ★★ same residue
- RELA p.His88fs Likely pathogenic same condition
- RELA p.Arg236Ter Pathogenic/Likely pathogenic ★★ same condition
- RELA c.1034-2A>C Likely pathogenic ★ same condition
- RELA p.Gln442Ter Conflicting classifications of pathogenicity ★ ⚠ same condition
- RELA p.Gln508His Likely benign same condition
- RELA p.Gln389fs Pathogenic/Likely pathogenic ★★ same type
- RELA p.Ala11fs 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/rela-p-ala345fs (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown