ABCG5 p.Ser46=
c.138C>T · rs775574718 · VCV2154659
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
ultra-rare (popmax 0.017%, mid)
Conditions
2
Cardiovascular phenotype
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 -1.7 | GERP -3.2 |
| Overall | ||
| CADD | 7.507 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.017%
Middle Eastern · 1/5,886 alleles
Filtering AF
0.00115%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.000974%
Overall
0.00168%
27/1,602,904 alleles · ultra-rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Middle Easterngrpmax | 0.017% | 5,886 |
| Remaining individualsnot grpmax-eligible | 0.00323% | 31,002 |
| South Asian | 0.00224% | 44,562 |
| European (non-Finnish) | 0.00179% | 55,978 |
| Admixed American | 0.00171% | 58,516 |
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
- ABCG5
- Protein
- p.Ser46=
- Coding
- c.138C>T
- MANE Select
- NM_022436
- dbSNP
- rs775574718
- Type
- single nucleotide variant
- Location
- chr2:43838542 (GRCh38)
- Gene constraint
- LOEUF 1.219 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
- Structure
- AlphaFold pLDDT 85.48 · 8 PDB
Similar variants
- ABCG5 p.Ser46fs Pathogenic ★★ same residue
- ABCG5 c.1325-1G>T Likely pathogenic ★★ same condition
- ABCG5 c.1762+1G>A Pathogenic/Likely pathogenic ★★ same condition
- ABCG5 c.634+1G>C Likely pathogenic ★★ same condition
- ABCG5 c.904+1G>A Pathogenic ★★ same condition
- ABCG5 p.Arg183Ter Pathogenic/Likely pathogenic ★★ same condition
- ABCG5 p.Arg243Ter Pathogenic ★★ same condition
- ABCG5 p.Arg389His Pathogenic/Likely 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/abcg5-p-ser46 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown