C3 p.Val901Ala
c.2702T>C · VCV4741980
Uncertain significance
Single submitter
Classification
Uncertain significance
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
AlphaMissense
likely pathogenic
0.7618 · ACMG-weighted
gnomAD v4.1
Absent
absent from gnomAD v4.1
Missense predictors
1/2 damaging
AlphaMissense, SaProt · REVEL no call
Computational evidence
| Protein change | ||
| AlphaMissense | 0.7618 | likely pathogenic |
|---|---|---|
| REVEL | 0.385 | indeterminate |
| SaProt | LLR -9.63 | tolerated |
| ⇒ AlphaMissense calls this damaging; SaProt does not; REVEL makes no call. | ||
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
| Constraint at this position | ||
| Conservation | phyloP 8.7 | GERP 1.8, phastCons 1 |
| Regional constraint | o/e 0.74 | unconstrained · MANE · 35 kb · p 3.5e-28 · regional, not allelic |
| Overall | ||
| CADD | 22.0 | PHRED · no single calibrated threshold — expert panels disagree |
AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.
Population frequency
gnomAD v4.1 · exomes + genomes
Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.
Variant & gene context
- Gene
- C3
- Protein
- p.Val901Ala
- Coding
- c.2702T>C
- MANE Select
- NM_000064
- Type
- single nucleotide variant
- Location
- chr19:6697438 (GRCh38)
- Gene constraint
- LOEUF 0.541 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 79.84 · 80 PDB
- Residue 901
- a β-strand
Similar variants
- C3 p.Val901Met Uncertain significance ★★ same residue
- C3 c.1003+1G>A Pathogenic/Likely pathogenic ★★ same type
- C3 c.2863+1G>T Likely pathogenic ★★ same type
- C3 c.4030-2A>G Likely pathogenic ★★ same type
- C3 p.Arg161Trp Pathogenic/Likely pathogenic ★★ ⚠ same type
- C3 p.Arg592Gln Pathogenic/Likely pathogenic ★★ ⚠ same type
- C3 p.Arg592Trp Likely pathogenic ★★ ⚠ same type
- C3 p.Arg764Ter Pathogenic/Likely pathogenic ★★ 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/c3-p-val901ala (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown