C8A p.Ala478=
c.1434C>G · rs537553560 · VCV1536204
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.0154%, sas)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Splicing | ||
| SpliceAI | <0.2 | no splice effect predicted · four deltas, not one · how we know |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP -1 | GERP -1.9 |
| Overall | ||
| CADD | 4.445 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0154%
South Asian · 14/91,086 alleles
Filtering AF
0.00919%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00735%
Overall
0.00613%
99/1,614,238 alleles · ultra-rare
exomes 93/1,461,878 · genomes 6/152,360 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| South Asiangrpmax | 0.0154% | 6,506 |
| European (non-Finnish) | 0.00695% | 14,391 |
| Remaining individualsnot grpmax-eligible | 0.0032% | 31,255 |
| East Asian | 0.00223% | 44,884 |
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.Ala478=
- Coding
- c.1434C>G
- MANE Select
- NM_000562
- dbSNP
- rs537553560
- Type
- single nucleotide variant
- Location
- chr1:56912456 (GRCh38)
- Gene constraint
- LOEUF 1.168 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 79.58 · 11 PDB
- Residue 478
- a UniProt-annotated variant site (in c8d1); the macpf domain; an α-helix
Similar variants
- 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
- C8A p.Arg207Gln 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-ala478 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown