C5 p.Pro1038Thr
c.3112C>A · VCV4810855
Uncertain significance
Single submitter
Classification
Uncertain significance
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
AlphaMissense
likely benign
0.0601 · ACMG-weighted
gnomAD v4.1
Absent
absent from gnomAD v4.1
Missense predictors
1/3 damaging
AlphaMissense, REVEL, SaProt
Computational evidence
| Protein change | ||
| AlphaMissense | 0.0601 | likely benign |
|---|---|---|
| REVEL | 0.043 | moderately benign-leaning |
| SaProt | LLR -11.16 | damaging |
| ⇒ SaProt calls this damaging; AlphaMissense and REVEL do not. | ||
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
| Constraint at this position | ||
| Conservation | phyloP 0.31 | GERP -2.2, phastCons 0.001 |
| Regional constraint | o/e 0.86 | unconstrained · MANE · 98 kb · p 1.2e-09 · regional, not allelic |
| Overall | ||
| CADD | 0.01 | 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
- C5
- Protein
- p.Pro1038Thr
- Coding
- c.3112C>A
- MANE Select
- NM_001735
- Type
- single nucleotide variant
- Location
- chr9:120989610 (GRCh38)
- Gene constraint
- LOEUF 0.779 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 81.67 · 49 PDB
- Residue 1038
- an α-helix; 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-pro1038thr (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown