CD46 p.Ser265=
c.795C>T · VCV3606553
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.00439%, sas)
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 -6.1 | GERP -3.7 |
| Overall | ||
| CADD | 3.131 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00439%
South Asian · 4/91,076 alleles
Filtering AF
0.00143%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.000891%
Overall
0.000558%
9/1,613,672 alleles · very rare
exomes 8/1,461,558 · genomes 1/152,114 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| South Asiangrpmax | 0.00439% | 22,769 |
| East Asian | 0.00223% | 44,868 |
| African / African-American | 0.00134% | 74,898 |
| European (non-Finnish) | 0.000254% | 393,252 |
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.Ser265=
- Coding
- c.795C>T
- MANE Select
- NM_172351
- Type
- single nucleotide variant
- Location
- chr1:207767134 (GRCh38)
- Gene constraint
- LOEUF 0.763 · pLI 0.04 (gnomAD)
- Structure
- AlphaFold pLDDT 82.38 · 7 PDB
- Residue 265
- the sushi 4 domain
Similar variants
- CD46 p.Ser265Asn Uncertain significance ★ ⚠ same residue
- CD46 c.1082+2T>A Pathogenic ★★ same type
- CD46 c.286+1G>C Pathogenic/Likely pathogenic ★★ same type
- CD46 c.286+2T>G Pathogenic/Likely pathogenic ★★ same type
- CD46 c.287-2A>G Pathogenic/Likely pathogenic ★★ same type
- CD46 p.Arg229Ter Pathogenic/Likely pathogenic ★★ same type
- CD46 p.Arg59Ter Pathogenic/Likely pathogenic ★★ same type
- CD46 p.Phe242Cys 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/cd46-p-ser265 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown