C8A p.Leu197=
c.591C>G · rs116129675 · VCV1164180
Benign/Likely benign
Multiple submitters
Classification
Benign/Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 5 submitters
gnomAD v4.1
Common
common (popmax 11.3%, sas) — 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 -0.93 | GERP -3.8, phastCons 0.002 |
| Overall | ||
| CADD | 1.535 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
11.3%
South Asian · 10,292/91,080 alleles
Filtering AF
11.1%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 11%
Overall
1.38%
22,258/1,613,790 alleles · common
| Ancestry group | Frequency | 1 in |
|---|---|---|
| South Asiangrpmax | 11.3% | 9 |
| Middle Eastern | 1.94% | 52 |
| Ashkenazi Jewishnot grpmax-eligible | 1.61% | 62 |
| Remaining individualsnot grpmax-eligible | 1.47% | 68 |
| European (non-Finnish) | 0.837% | 119 |
| Admixed American | 0.345% | 290 |
| Finnishnot grpmax-eligible | 0.339% | 295 |
| African / African-American | 0.14% | 714 |
| East Asian | 0.111% | 897 |
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.Leu197=
- Coding
- c.591C>G
- MANE Select
- NM_000562
- dbSNP
- rs116129675
- Type
- single nucleotide variant
- Location
- chr1:56881571 (GRCh38)
- Gene constraint
- LOEUF 1.168 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 79.58 · 11 PDB
- Residue 197
- a β-strand; the macpf domain
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-leu197 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown