ABCG5 p.Ile562=
c.1686C>A · rs538393765 · VCV1778006
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
ultra-rare (popmax 0.0166%, sas)
Conditions
1
Cardiovascular phenotype
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation/SpliceAI carries the signal. | ||
| Splicing | ||
| SpliceAI | Δ0.32 | acceptor loss · deltas |
|---|---|---|
| Pangolin | Δ0.36 | loss · gain 0.03 · agrees with SpliceAI · independent |
| Constraint at this position | ||
| Conservation | phyloP 1.3 | GERP -0.033, phastCons 0.98 |
| Overall | ||
| CADD | 1.493 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0166%
South Asian · 15/90,210 alleles
Filtering AF
0.0102%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00828%
Overall
0.00118%
19/1,606,958 alleles · ultra-rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| South Asiangrpmax | 0.0166% | 6,014 |
| East Asian | 0.00671% | 14,900 |
| Remaining individualsnot grpmax-eligible | 0.00161% | 62,278 |
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.Ile562=
- Coding
- c.1686C>A
- MANE Select
- NM_022436
- dbSNP
- rs538393765
- Type
- single nucleotide variant
- Location
- chr2:43814553 (GRCh38)
- Gene constraint
- LOEUF 1.219 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
- Structure
- AlphaFold pLDDT 85.48 · 8 PDB
- Residue 562
- the abc transmembrane type-2 domain; an α-helix
Similar variants
- ABCG5 c.1325-1G>T Likely pathogenic ★★ same condition
- ABCG5 p.Gln251Ter Pathogenic ★★ same condition
- ABCG5 p.Glu146Ter Pathogenic ★★ same condition
- ABCG5 p.Ala170Asp Uncertain significance ★★ ⚠ same condition
- ABCG5 p.Ala264Val Uncertain significance ★★ ⚠ same condition
- ABCG5 p.Ala278Glu Uncertain significance ★★ ⚠ same condition
- ABCG5 p.Ala333Ser Uncertain significance ★★ ⚠ same condition
- ABCG5 p.Ala429Thr Uncertain significance ★★ ⚠ 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-ile562 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown