ABCG1 p.Leu643=
c.1929C>T · rs200531217 · VCV740389
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 3 submitters
gnomAD v4.1
Rare
rare (popmax 0.544%, 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 -0.75 | GERP -4, phastCons 0.001 |
| Overall | ||
| CADD | 1.113 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.544%
Middle Eastern · 33/6,062 alleles
Filtering AF
0.398%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.348%
Overall
0.0317%
512/1,614,138 alleles · rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Middle Easterngrpmax | 0.544% | 184 |
| Ashkenazi Jewishnot grpmax-eligible | 0.524% | 191 |
| South Asian | 0.134% | 747 |
| Remaining individualsnot grpmax-eligible | 0.04% | 2,500 |
| Admixed American | 0.025% | 4,002 |
| African / African-American | 0.016% | 6,252 |
| European (non-Finnish) | 0.0125% | 7,973 |
| East Asian | 0.00223% | 44,884 |
| Finnishnot grpmax-eligible | 0.00156% | 64,020 |
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.Leu643=
- Coding
- c.1929C>T
- MANE Select
- NM_016818
- dbSNP
- rs200531217
- Type
- single nucleotide variant
- Location
- chr21:42296320 (GRCh38)
- Gene constraint
- LOEUF 0.573 · pLI 0.20 (gnomAD)
- Structure
- AlphaFold pLDDT 81.34 · 5 PDB
- Residue 643
- the abc transmembrane type-2 domain
Similar variants
- ABCG1 p.Ala456= 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
- ABCG1 c.1122+2T>C Uncertain significance ★ ⚠ same type
- ABCG1 p.Ala546Thr Uncertain significance ★ ⚠ same type
- ABCG1 p.Arg222Cys 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-leu643 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown