ABCG1 p.Ser408=
c.1224G>A · rs141061143 · VCV2652705
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.0957%, afr)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| REVEL | 0.137 | moderately benign-leaning |
|---|---|---|
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
| Constraint at this position | ||
| Conservation | phyloP 6.5 | GERP 0.84, phastCons 1 |
| Overall | ||
| CADD | 21.6 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0957%
African / African-American · 69/72,104 alleles
Filtering AF
0.0776%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0709%
Overall
0.0128%
203/1,589,610 alleles · ultra-rare
exomes 154/1,455,508 · genomes 49/134,102 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 0.0957% | 1,045 |
| Middle Eastern | 0.0664% | 1,505 |
| Admixed American | 0.0259% | 3,859 |
| Remaining individualsnot grpmax-eligible | 0.0193% | 5,168 |
| European (non-Finnish) | 0.00876% | 11,422 |
| East Asian | 0.00227% | 44,150 |
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
- ABCG1
- Protein
- p.Ser408=
- Coding
- c.1224G>A
- MANE Select
- NM_016818
- dbSNP
- rs141061143
- Type
- single nucleotide variant
- Location
- chr21:42288312 (GRCh38)
- Gene constraint
- LOEUF 0.573 · pLI 0.20 (gnomAD)
- Structure
- AlphaFold pLDDT 81.34 · 5 PDB
- Residue 408
- an α-helix
Similar variants
- ABCG1 p.Ser408Leu Uncertain significance ★ ⚠ same residue
- ABCG1 p.Ser408Trp Uncertain significance ★ same residue
- ABCG1 p.Ala456= Benign ★★ same type
- ABCG1 p.Leu643= Likely benign ★★ same type
- ABCG1 p.Pro149= Benign ★★ same type
- ABCG1 p.Ser547= Benign ★★ same type
- ABCG1 c.1122+21A>C Uncertain significance ★ ⚠ same type
- ABCG1 c.1122+24G>C Uncertain significance ★ ⚠ 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/abcg1-p-ser408 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown