RELB p.His215=
c.645C>T · rs774779724 · VCV1631805
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.066%, mid)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Splicing | ||
| SpliceAI | <0.2 | all four deltas below 0.2 · C>G here scores Δ0.63 · evaluated, not missing |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP -5.4 | GERP -4.8 |
| Overall | ||
| CADD | 5.987 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.066%
Middle Eastern · 4/6,062 alleles
Filtering AF
0.0225%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0135%
Overall
0.00249%
40/1,603,826 alleles · ultra-rare
exomes 37/1,451,628 · genomes 3/152,198 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Middle Easterngrpmax | 0.066% | 1,516 |
| African / African-American | 0.012% | 8,307 |
| East Asian | 0.00899% | 11,128 |
| Remaining individualsnot grpmax-eligible | 0.00804% | 12,444 |
| South Asian | 0.00551% | 18,140 |
| Admixed American | 0.00335% | 29,832 |
| European (non-Finnish) | 0.000934% | 107,025 |
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.His215=
- Coding
- c.645C>T
- MANE Select
- NM_006509
- dbSNP
- rs774779724
- Type
- single nucleotide variant
- Location
- chr19:45022193 (GRCh38)
- Gene constraint
- LOEUF 0.512 · pLI 0.97 (gnomAD)
- Structure
- AlphaFold pLDDT 70.42 · 1 PDB
- Residue 215
- the rhd domain
Similar variants
- RELB p.His215Gln 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-his215 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown