Benign/Likely benign
Multiple submitters
Classification
Benign/Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 8 submitters
gnomAD v4.1
Common
common (popmax 14.1%, afr) — too common for a highly-penetrant pathogenic allele
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 -3.1, phastCons 0.006 |
| Overall | ||
| CADD | 5.182 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
14.1%
African / African-American · 10,479/74,444 alleles
Filtering AF
13.9%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 13.8%
Overall
10.1%
163,154/1,607,578 alleles · common
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 14.1% | 7 |
| European (non-Finnish) | 10.8% | 9 |
| Remaining individualsnot grpmax-eligible | 9.56% | 10 |
| South Asian | 8.1% | 12 |
| Admixed American | 7.1% | 14 |
| Middle Eastern | 6.56% | 15 |
| Finnishnot grpmax-eligible | 6.44% | 16 |
| Ashkenazi Jewishnot grpmax-eligible | 6.14% | 16 |
| Amishnot grpmax-eligible | 3.51% | 29 |
| East Asian | 2.9% | 34 |
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
- C5
- Protein
- p.Thr487=
- Coding
- c.1461C>T
- MANE Select
- NM_001735
- dbSNP
- rs2230214
- Type
- single nucleotide variant
- Location
- chr9:121020021 (GRCh38)
- Gene constraint
- LOEUF 0.779 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 81.67 · 49 PDB
- Residue 487
- a β-strand; a UniProt-annotated variant site (in c5d)
Similar variants
- C5 c.2257+1G>A Likely pathogenic ★★ same type
- C5 c.4679-2A>G Likely pathogenic ★★ same type
- C5 p.Arg1476Ter Pathogenic/Likely pathogenic ★★ same type
- C5 p.Gln19Ter Pathogenic ★★ same type
- C5 p.Glu1437Ter Pathogenic/Likely pathogenic ★★ same type
- C5 p.Trp469Ter Pathogenic/Likely pathogenic ★★ same type
- C5 c.2059+3A>G Uncertain significance ★★ same type
- C5 c.3391-13T>A 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/c5-p-thr487 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown