Benign/Likely benign
Multiple submitters
Classification
Benign/Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 6 submitters
gnomAD v4.1
Common
common (popmax 22.1%, 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 -0.43 | GERP -2.4, phastCons 0.059 |
| Overall | ||
| CADD | 6.44 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
22.1%
African / African-American · 16,593/75,028 alleles
Filtering AF
21.8%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 21.7%
Overall
6.2%
100,133/1,614,104 alleles · common
exomes 84,518/1,461,820 · genomes 15,615/152,284 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 22.1% | 5 |
| South Asian | 13.3% | 8 |
| Middle Eastern | 11.3% | 9 |
| Admixed American | 9.67% | 10 |
| Remaining individualsnot grpmax-eligible | 6.89% | 15 |
| East Asian | 6.35% | 16 |
| Amishnot grpmax-eligible | 4.82% | 21 |
| Finnishnot grpmax-eligible | 4.61% | 22 |
| European (non-Finnish) | 4.54% | 22 |
| Ashkenazi Jewishnot grpmax-eligible | 4.29% | 23 |
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
- C8A
- Protein
- p.Pro501=
- Coding
- c.1503T>C
- MANE Select
- NM_000562
- dbSNP
- rs1754533
- Type
- single nucleotide variant
- Location
- chr1:56912525 (GRCh38)
- Gene constraint
- LOEUF 1.168 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 79.58 · 11 PDB
- Residue 501
- the egf-like domain; a UniProt-annotated variant site (in c8d1)
Similar variants
- C8A p.Pro501Thr Uncertain significance ★ ⚠ same residue
- C8A p.Arg424Ter Pathogenic ★★ same type
- C8A p.Arg498Ter Pathogenic/Likely pathogenic ★★ same type
- C8A p.Glu466Ter Pathogenic ★★ same type
- C8A p.Tyr210Ter Pathogenic/Likely pathogenic ★★ same type
- C8A p.Tyr384Ter Pathogenic/Likely pathogenic ★★ same type
- C8A p.Arg107Cys Uncertain significance ★★ ⚠ same type
- C8A p.Arg196His 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/c8a-p-pro501 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown