RELB p.Pro439=
c.1317G>A · rs369885274 · VCV1586955
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 3 submitters
gnomAD v4.1
Rare
rare (popmax 0.126%, amr)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Splicing | ||
| SpliceAI | <0.2 | no splice effect predicted · four deltas, not one · how we know |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP -4 | GERP -3.4 |
| Overall | ||
| CADD | 2.53 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.126%
Admixed American · 75/59,334 alleles
Filtering AF
0.103%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0949%
Overall
0.0171%
275/1,609,900 alleles · rare
exomes 228/1,457,740 · genomes 47/152,160 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Admixed Americangrpmax | 0.126% | 791 |
| European (non-Finnish) | 0.0154% | 6,474 |
| Remaining individualsnot grpmax-eligible | 0.00802% | 12,472 |
| South Asian | 0.00776% | 12,893 |
| African / African-American | 0.00668% | 14,962 |
| Finnishnot grpmax-eligible | 0.00157% | 63,734 |
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
- RELB
- Protein
- p.Pro439=
- Coding
- c.1317G>A
- MANE Select
- NM_006509
- dbSNP
- rs369885274
- Type
- single nucleotide variant
- Location
- chr19:45034491 (GRCh38)
- Gene constraint
- LOEUF 0.512 · pLI 0.97 (gnomAD)
- Structure
- AlphaFold pLDDT 70.42 · 1 PDB
- Residue 439
- the rhd domain; a UniProt-annotated variant site (in imd53)
Similar variants
- RELB p.Pro439Leu 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
- RELB p.Arg213Trp Uncertain significance ★★ ⚠ same type
- RELB p.Arg219Gln 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-pro439 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown