C5 p.Leu152=
c.456G>A · rs770873543 · VCV1574506
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.0312%, sas)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation/SpliceAI carries the signal. | ||
| Splicing | ||
| SpliceAI | Δ0.30 | acceptor loss · deltas |
|---|---|---|
| Pangolin | Δ0.20 | loss · gain 0.00 · agrees with SpliceAI · independent |
| Constraint at this position | ||
| Conservation | phyloP 0.26 | GERP 0.86, phastCons 0.97 |
| Overall | ||
| CADD | 5.606 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0312%
South Asian · 26/83,366 alleles
Filtering AF
0.0218%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0187%
Overall
0.00182%
28/1,535,362 alleles · ultra-rare
exomes 26/1,383,306 · genomes 2/152,056 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| South Asiangrpmax | 0.0312% | 3,206 |
| Remaining individualsnot grpmax-eligible | 0.00338% | 29,624 |
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.Leu152=
- Coding
- c.456G>A
- MANE Select
- NM_001735
- dbSNP
- rs770873543
- Type
- single nucleotide variant
- Location
- chr9:121037917 (GRCh38)
- Gene constraint
- LOEUF 0.779 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 81.67 · 49 PDB
- Residue 152
- a UniProt-annotated variant site (in c5d); a β-strand
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-leu152 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown