C5 p.Val375=
c.1125T>G · rs778186090 · VCV1610830
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
ultra-rare (popmax 0.0117%, amr)
Conditions
2
Eculizumab, poor response to
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 -1.2 | GERP -2.7 |
| Overall | ||
| CADD | 3.448 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0117%
Admixed American · 7/60,034 alleles
Filtering AF
0.00543%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0038%
Overall
0.000434%
7/1,613,254 alleles · ultra-rare
exomes 7/1,460,908 · genomes 0/152,346 · joint denominator
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.Val375=
- Coding
- c.1125T>G
- MANE Select
- NM_001735
- dbSNP
- rs778186090
- Type
- single nucleotide variant
- Location
- chr9:121021686 (GRCh38)
- Gene constraint
- LOEUF 0.779 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 81.67 · 49 PDB
- Residue 375
- a UniProt-annotated variant site (in c5d); a β-strand
Similar variants
- C5 c.2257+1G>A Likely pathogenic ★★ same condition
- C5 c.4679-2A>G Likely pathogenic ★★ same condition
- C5 p.Arg1476Ter Pathogenic/Likely pathogenic ★★ same condition
- C5 p.Gln19Ter Pathogenic ★★ same condition
- C5 p.Trp469Ter Pathogenic/Likely pathogenic ★★ same condition
- C5 c.2059+3A>G Uncertain significance ★★ same condition
- C5 c.4081-6A>G Uncertain significance ★★ same condition
- C5 c.4504+4A>G Uncertain significance ★★ same condition
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-val375 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown