CD46 p.Phe125=
c.375T>C · rs554142324 · VCV1633888
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.0067%, amr)
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 0.24 | GERP -2.3 |
| Overall | ||
| CADD | 3.042 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0067%
Admixed American · 4/59,718 alleles
Filtering AF
0.00226%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00135%
Overall
0.000249%
4/1,604,762 alleles · very rare
exomes 2/1,452,432 · genomes 2/152,330 · joint denominator
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.Phe125=
- Coding
- c.375T>C
- MANE Select
- NM_172351
- dbSNP
- rs554142324
- Type
- single nucleotide variant
- Location
- chr1:207757628 (GRCh38)
- Gene constraint
- LOEUF 0.763 · pLI 0.04 (gnomAD)
- Structure
- AlphaFold pLDDT 82.38 · 7 PDB
- Residue 125
- the sushi 2 domain; a β-strand
Similar variants
- 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
- CD46 p.Trp276Ter 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-phe125 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown