C5 p.Ile325=
c.975T>A · rs370834994 · VCV1482689
Conflicting classifications of pathogenicity
Conflicting submitters
Classification
Conflicting classifications of pathogenicity
ClinVar
Review
Conflicting submitters ★☆☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
very rare (popmax 0.000509%, nfe)
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 0.36 | GERP 1.7, phastCons 0.56 |
| Overall | ||
| CADD | 8.424 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.000509%
European (non-Finnish) · 6/1,178,828 alleles
Filtering AF
0.000183%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00012%
Overall
0.000373%
6/1,610,632 alleles · very rare
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.Ile325=
- Coding
- c.975T>A
- MANE Select
- NM_001735
- dbSNP
- rs370834994
- Type
- single nucleotide variant
- Location
- chr9:121025479 (GRCh38)
- Gene constraint
- LOEUF 0.779 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 81.67 · 49 PDB
- Residue 325
- 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-ile325 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown