RELA p.Pro521=
c.1563G>A · rs376881598 · VCV2082499
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.0102%, nfe)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP -3.9 | GERP -3.7 |
| Overall | ||
| CADD | 0.403 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0102%
European (non-Finnish) · 120/1,176,402 alleles
Filtering AF
0.0087%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00814%
Overall
0.00811%
130/1,603,808 alleles · ultra-rare
exomes 120/1,451,624 · genomes 10/152,184 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| European (non-Finnish)grpmax | 0.0102% | 9,803 |
| Remaining individualsnot grpmax-eligible | 0.00646% | 15,480 |
| Admixed American | 0.00525% | 19,047 |
| African / African-American | 0.0027% | 37,078 |
| South Asian | 0.00111% | 89,734 |
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.Pro521=
- Coding
- c.1563G>A
- MANE Select
- NM_021975
- dbSNP
- rs376881598
- Type
- single nucleotide variant
- Location
- chr11:65654471 (GRCh38)
- Gene constraint
- LOEUF 0.4 · pLI 1.00 (gnomAD)
- Structure
- AlphaFold pLDDT 73.52 · 88 PDB
- Residue 521
- a UniProt-annotated variant site (found in a patient diagnosed with autoimmune lymphoproliferative syndrome; uncertain significance); the 'disordered' region; the 'transcriptional activation domain 2' region
Similar variants
- 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
- RELA p.Ala538Thr 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-pro521 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown