C5 p.Ala1422=
c.4266G>A · rs12237774 · VCV1167627
Benign
Multiple submitters
Classification
Benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 5 submitters
gnomAD v4.1
Common
common (popmax 21.3%, eas) — 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 -2.4 | GERP -4.2 |
| Overall | ||
| CADD | 6.613 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
21.3%
East Asian · 9,533/44,826 alleles
Filtering AF
20.9%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 20.8%
Overall
2.92%
47,165/1,613,500 alleles · common
exomes 36,327/1,461,406 · genomes 10,838/152,094 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| East Asiangrpmax | 21.3% | 5 |
| African / African-American | 18.9% | 5 |
| Remaining individualsnot grpmax-eligible | 4.05% | 25 |
| South Asian | 4.05% | 25 |
| Admixed American | 3% | 33 |
| Finnishnot grpmax-eligible | 2.61% | 38 |
| Middle Eastern | 2.29% | 44 |
| Ashkenazi Jewishnot grpmax-eligible | 1.85% | 54 |
| European (non-Finnish) | 1.11% | 90 |
| Amishnot grpmax-eligible | 0.329% | 304 |
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.Ala1422=
- Coding
- c.4266G>A
- MANE Select
- NM_001735
- dbSNP
- rs12237774
- Type
- single nucleotide variant
- Location
- chr9:120963693 (GRCh38)
- Gene constraint
- LOEUF 0.779 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 81.67 · 49 PDB
- Residue 1422
- 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-ala1422 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown