CD46 p.Ser151=
c.453C>T · rs145041158 · VCV876703
Benign
Multiple submitters
Classification
Benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 9 submitters
gnomAD v4.1
Rare
low-frequency (popmax 3.76%, eas)
Conditions
2
atypical hemolytic-uremic syndrome with MCP/CD46 anomaly
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Splicing | ||
| SpliceAI | <0.2 | all four deltas below 0.2 · C>A here scores Δ0.47 · evaluated, not missing |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP -3.9 | GERP -3.1 |
| Overall | ||
| CADD | 4.536 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
3.76%
East Asian · 1,683/44,726 alleles
Filtering AF
3.61%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 3.55%
Overall
0.275%
4,417/1,604,142 alleles · low-frequency
exomes 3,740/1,451,952 · genomes 677/152,190 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| East Asiangrpmax | 3.76% | 27 |
| Admixed American | 1.26% | 79 |
| African / African-American | 0.695% | 144 |
| Remaining individualsnot grpmax-eligible | 0.324% | 309 |
| South Asian | 0.258% | 388 |
| European (non-Finnish) | 0.0866% | 1,155 |
| Middle Eastern | 0.0331% | 3,024 |
| Finnishnot grpmax-eligible | 0.00782% | 12,792 |
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
- CD46
- Protein
- p.Ser151=
- Coding
- c.453C>T
- MANE Select
- NM_172351
- dbSNP
- rs145041158
- Type
- single nucleotide variant
- Location
- chr1:207759702 (GRCh38)
- Gene constraint
- LOEUF 0.763 · pLI 0.04 (gnomAD)
- Structure
- AlphaFold pLDDT 82.38 · 7 PDB
- Residue 151
- the sushi 2 domain; a β-strand
Similar variants
- CD46 c.1082+2T>A Pathogenic ★★ same condition
- CD46 c.286+1G>C Pathogenic/Likely pathogenic ★★ same condition
- CD46 c.286+2T>G Pathogenic/Likely pathogenic ★★ same condition
- CD46 c.287-2A>G Pathogenic/Likely pathogenic ★★ same condition
- CD46 p.Arg229Ter Pathogenic/Likely pathogenic ★★ same condition
- CD46 p.Arg59Ter Pathogenic/Likely pathogenic ★★ same condition
- CD46 p.Phe242Cys Pathogenic/Likely pathogenic ★★ same condition
- CD46 p.Trp276Ter Pathogenic ★★ 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/cd46-p-ser151 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown