RELA p.Ala345=
c.1035A>G · rs187885211 · VCV2641966
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
very rare (popmax 0.00674%, nfe)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| REVEL | 0.047 | moderately benign-leaning |
|---|---|---|
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
| Constraint at this position | ||
| Conservation | phyloP 0.26 | GERP -3.7, phastCons 0.84 |
| Overall | ||
| CADD | 6.195 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00674%
European (non-Finnish) · 79/1,171,408 alleles
Filtering AF
0.0055%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00509%
Overall
0.00508%
81/1,594,620 alleles · very rare
exomes 79/1,442,480 · genomes 2/152,140 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| European (non-Finnish)grpmax | 0.00674% | 14,828 |
| Remaining individualsnot grpmax-eligible | 0.00161% | 61,954 |
| African / African-American | 0.00134% | 74,868 |
Rarity supports pathogenicity (ACMG PM2); frequency above a disease-specific BA1/BS1 threshold argues against it. A variant frequent in one ancestry group can be near-absent in others, so a single global figure can mislead.
Variant & gene context
- Gene
- RELA
- Protein
- p.Ala345=
- Coding
- c.1035A>G
- MANE Select
- NM_021975
- dbSNP
- rs187885211
- Type
- single nucleotide variant
- Location
- chr11:65654999 (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)
Similar variants
- RELA p.Ala345fs Likely pathogenic ★ same residue
- RELA p.Arg198Ter Pathogenic/Likely pathogenic ★★ same type
- RELA p.Arg236Ter Pathogenic/Likely pathogenic ★★ same type
- RELA p.Arg329Ter Pathogenic/Likely pathogenic ★★ same type
- RELA p.Gln372Ter Pathogenic/Likely pathogenic ★★ same type
- RELA p.Ala264Val Uncertain significance ★★ ⚠ same type
- RELA p.Ala404Pro Uncertain significance ★★ ⚠ same type
- RELA p.Ala404Thr 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/rela-p-ala345 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown