C8A p.Arg422=
c.1266G>A · rs752889473 · VCV1933934
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.0516%, sas)
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 -0.11 | GERP -3.6 |
| Overall | ||
| CADD | 2.691 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0516%
South Asian · 47/91,078 alleles
Filtering AF
0.0399%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0357%
Overall
0.00322%
52/1,614,042 alleles · ultra-rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| South Asiangrpmax | 0.0516% | 1,938 |
| Remaining individualsnot grpmax-eligible | 0.008% | 12,498 |
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.Arg422=
- Coding
- c.1266G>A
- MANE Select
- NM_000562
- dbSNP
- rs752889473
- Type
- single nucleotide variant
- Location
- chr1:56907999 (GRCh38)
- Gene constraint
- LOEUF 1.168 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 79.58 · 11 PDB
- Residue 422
- the macpf domain
Similar variants
- C8A p.Arg422Trp Uncertain significance ★★ ⚠ same residue
- C8A p.Arg422Gln 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
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-arg422 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown