RELB p.Arg563=
c.1689C>T · rs556023428 · VCV1446718
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 3 submitters
gnomAD v4.1
Rare
ultra-rare (popmax 0.0745%, mid)
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 |
|---|---|---|
| Pangolin | Δ0.34 | gain · loss 0.00 · not in the SpliceAI release · independent |
| Constraint at this position | ||
| Conservation | phyloP -2.3 | GERP -4 |
| Overall | ||
| CADD | 9.523 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0745%
Middle Eastern · 4/5,370 alleles
Filtering AF
0.0254%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0153%
Overall
0.00161%
24/1,492,928 alleles · ultra-rare
exomes 22/1,340,616 · genomes 2/152,312 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Middle Easterngrpmax | 0.0745% | 1,342 |
| East Asian | 0.0102% | 9,816 |
| South Asian | 0.00537% | 18,611 |
| Remaining individualsnot grpmax-eligible | 0.00176% | 56,946 |
| European (non-Finnish) | 0.000978% | 102,209 |
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
- RELB
- Protein
- p.Arg563=
- Coding
- c.1689C>T
- MANE Select
- NM_006509
- dbSNP
- rs556023428
- Type
- single nucleotide variant
- Location
- chr19:45037739 (GRCh38)
- Gene constraint
- LOEUF 0.512 · pLI 0.97 (gnomAD)
- Structure
- AlphaFold pLDDT 70.42 · 1 PDB
- Residue 563
- a UniProt-annotated variant site (in imd53)
Similar variants
- RELB p.Arg563Cys Uncertain significance ★★ ⚠ same residue
- RELB p.Arg563His Uncertain significance ★ ⚠ same residue
- RELB p.Arg563Ser Uncertain significance ★ ⚠ same residue
- RELB p.Ala541Asp Uncertain significance ★★ ⚠ same type
- RELB p.Ala565Val Uncertain significance ★★ ⚠ same type
- RELB p.Arg176Gln Uncertain significance ★★ ⚠ same type
- RELB p.Arg211Gln Uncertain significance ★★ ⚠ same type
- RELB p.Arg213Gln 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/relb-p-arg563 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown