C5 p.Val1361=
c.4083A>G · rs758685448 · VCV2167894
Conflicting classifications of pathogenicity
Conflicting submitters
Classification
Conflicting classifications of pathogenicity
ClinVar
Review
Conflicting submitters ★☆☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
ultra-rare (popmax 0.0824%, mid)
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 | GERP -0.69 |
| Overall | ||
| CADD | 6.932 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0824%
Middle Eastern · 5/6,068 alleles
Filtering AF
0.0324%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.021%
Overall
0.00143%
23/1,607,622 alleles · ultra-rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Middle Easterngrpmax | 0.0824% | 1,214 |
| Admixed American | 0.00667% | 15,001 |
| South Asian | 0.0044% | 22,729 |
| European (non-Finnish) | 0.000852% | 117,437 |
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
- C5
- Protein
- p.Val1361=
- Coding
- c.4083A>G
- MANE Select
- NM_001735
- dbSNP
- rs758685448
- Type
- single nucleotide variant
- Location
- chr9:120970249 (GRCh38)
- Gene constraint
- LOEUF 0.779 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 81.67 · 49 PDB
- Residue 1361
- a β-strand; a disulfide bond; a UniProt-annotated variant site (in c5d)
Similar variants
- C5 c.2257+1G>A Likely pathogenic ★★ same type
- C5 c.4679-2A>G Likely pathogenic ★★ same type
- C5 p.Arg1476Ter Pathogenic/Likely pathogenic ★★ same type
- C5 p.Gln19Ter Pathogenic ★★ same type
- C5 p.Glu1437Ter Pathogenic/Likely pathogenic ★★ same type
- C5 p.Trp469Ter Pathogenic/Likely pathogenic ★★ same type
- C5 c.2059+3A>G Uncertain significance ★★ same type
- C5 c.3391-13T>A 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/c5-p-val1361 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown