C8A p.Lys242=
c.726A>G · rs781723718 · VCV1906644
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.0274%, 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 -3.7 | GERP -4.6 |
| Overall | ||
| CADD | 0.323 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0274%
South Asian · 25/91,090 alleles
Filtering AF
0.019%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0163%
Overall
0.00161%
26/1,614,058 alleles · ultra-rare
exomes 26/1,461,724 · genomes 0/152,334 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| South Asiangrpmax | 0.0274% | 3,644 |
| European (non-Finnish) | 8.47e-05% | 1,179,958 |
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.Lys242=
- Coding
- c.726A>G
- MANE Select
- NM_000562
- dbSNP
- rs781723718
- Type
- single nucleotide variant
- Location
- chr1:56883552 (GRCh38)
- Gene constraint
- LOEUF 1.168 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 79.58 · 11 PDB
- Residue 242
- an α-helix; 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-lys242 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown