RELA p.Pro486=
c.1458C>A · rs746579575 · VCV1595148
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.0176%, sas)
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 -0.38 | GERP -3.3 |
| Overall | ||
| CADD | 3.391 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0176%
South Asian · 16/90,998 alleles
Filtering AF
0.011%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00899%
Overall
0.00155%
25/1,613,492 alleles · ultra-rare
exomes 22/1,461,248 · genomes 3/152,244 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| South Asiangrpmax | 0.0176% | 5,687 |
| Middle Eastern | 0.0164% | 6,082 |
| African / African-American | 0.00667% | 14,986 |
| European (non-Finnish) | 0.000254% | 393,267 |
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.Pro486=
- Coding
- c.1458C>A
- MANE Select
- NM_021975
- dbSNP
- rs746579575
- Type
- single nucleotide variant
- Location
- chr11:65654576 (GRCh38)
- Gene constraint
- LOEUF 0.4 · pLI 1.00 (gnomAD)
- Structure
- AlphaFold pLDDT 73.52 · 88 PDB
- Residue 486
- a UniProt-annotated variant site (found in a patient diagnosed with autoimmune lymphoproliferative syndrome; uncertain significance)
Similar variants
- RELA p.Pro486Leu Uncertain significance ★★ ⚠ same residue
- RELA p.Pro486Arg Uncertain significance ★ ⚠ 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
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-pro486 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown