C9 p.Lys443=
c.1329G>A · rs1382253641 · VCV1630290
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.00187%, nfe)
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 -1.3 | GERP -4.2 |
| Overall | ||
| CADD | 1.524 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00187%
European (non-Finnish) · 22/1,179,354 alleles
Filtering AF
0.00122%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00104%
Overall
0.00149%
24/1,613,152 alleles · very rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| European (non-Finnish)grpmax | 0.00187% | 53,607 |
| Remaining individualsnot grpmax-eligible | 0.0016% | 62,440 |
| African / African-American | 0.00134% | 74,858 |
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
- C9
- Protein
- p.Lys443=
- Coding
- c.1329G>A
- MANE Select
- NM_001737
- dbSNP
- rs1382253641
- Type
- single nucleotide variant
- Location
- chr5:39306704 (GRCh38)
- Gene constraint
- LOEUF 1.223 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 79.32 · 9 PDB
- Residue 443
- the macpf domain; an α-helix
Similar variants
- C9 p.Lys443Met Uncertain significance ★ ⚠ same residue
- C9 c.871-2A>G Likely pathogenic ★★ same type
- C9 p.Arg116Ter Pathogenic/Likely pathogenic ★★ same type
- C9 p.Arg154Ter Pathogenic/Likely pathogenic ★★ same type
- C9 p.Arg194Ter Pathogenic/Likely pathogenic ★★ same type
- C9 p.Arg86Ter Pathogenic/Likely pathogenic ★★ same type
- C9 p.Cys54Ter Pathogenic/Likely pathogenic ★★ same type
- C9 c.1240+5G>T 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/c9-p-lys443 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown