CD46 p.Ala296=
c.888G>A · rs141930331 · VCV1586940
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 3 submitters
gnomAD v4.1
Rare
ultra-rare (popmax 0.0494%, mid)
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 -2 | GERP -3.4 |
| Overall | ||
| CADD | 3.727 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0494%
Middle Eastern · 3/6,076 alleles
Filtering AF
0.0134%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00716%
Overall
0.00596%
96/1,610,706 alleles · ultra-rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Middle Easterngrpmax | 0.0494% | 2,025 |
| African / African-American | 0.0147% | 6,795 |
| Admixed American | 0.0117% | 8,571 |
| Remaining individualsnot grpmax-eligible | 0.00641% | 15,592 |
| European (non-Finnish) | 0.00603% | 16,581 |
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.Ala296=
- Coding
- c.888G>A
- MANE Select
- NM_172351
- dbSNP
- rs141930331
- Type
- single nucleotide variant
- Location
- chr1:207767810 (GRCh38)
- Gene constraint
- LOEUF 0.763 · pLI 0.04 (gnomAD)
- Structure
- AlphaFold pLDDT 82.38 · 7 PDB
- Residue 296
- the 'disordered' region
Similar variants
- CD46 p.Ala296Val Uncertain significance ★★ ⚠ same residue
- CD46 p.Ala296Thr Uncertain significance ★ ⚠ same residue
- CD46 p.Ala296fs Pathogenic/Likely pathogenic ★★ 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
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-ala296 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown