C5AR2 p.Leu281=
c.843C>T · rs34085015 · VCV777502
Benign
Multiple submitters
Classification
Benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
low-frequency (popmax 2.16%, afr)
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 -6.2 | GERP -4.4 |
| Overall | ||
| CADD | 0.545 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
2.16%
African / African-American · 1,623/75,064 alleles
Filtering AF
2.07%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 2.04%
Overall
0.115%
1,861/1,614,082 alleles · low-frequency
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 2.16% | 46 |
| Admixed American | 0.197% | 509 |
| Remaining individualsnot grpmax-eligible | 0.146% | 687 |
| Middle Eastern | 0.0495% | 2,021 |
| South Asian | 0.00659% | 15,181 |
| European (non-Finnish) | 0.00169% | 59,001 |
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
- C5AR2
- Protein
- p.Leu281=
- Coding
- c.843C>T
- MANE Select
- NM_001271749
- dbSNP
- rs34085015
- Type
- single nucleotide variant
- Location
- chr19:47341642 (GRCh38)
- Gene constraint
- LOEUF 1.788 · pLI 0.37 (gnomAD)
- Structure
- AlphaFold pLDDT 86.24 · 7 PDB
Similar variants
- C5AR2 p.Leu281Phe Uncertain significance ★ ⚠ same residue
- C5AR2 p.Ile171Thr Uncertain significance ★★ ⚠ same type
- C5AR2 p.His329Arg Benign ★★ same type
- C5AR2 p.Leu299Val Benign/Likely benign ★★ same type
- C5AR2 p.Ser17= Benign ★★ same type
- C5AR2 p.Ala136Thr Uncertain significance ★ ⚠ same type
- C5AR2 p.Ala170Thr Uncertain significance ★ ⚠ same type
- C5AR2 p.Ala199Thr 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/c5ar2-p-leu281 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown