ABCG8 p.Leu336=
c.1006T>C · rs375507330 · VCV1786055
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.00668%, eas)
Conditions
1
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 0.59 | GERP -2.5 |
| Overall | ||
| CADD | 6.526 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00668%
East Asian · 3/44,886 alleles
Filtering AF
0.00177%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00104%
Overall
0.000744%
12/1,613,958 alleles · very rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| East Asiangrpmax | 0.00668% | 14,962 |
| African / African-American | 0.00534% | 18,735 |
| Remaining individualsnot grpmax-eligible | 0.0016% | 62,484 |
| European (non-Finnish) | 0.000339% | 295,010 |
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
- ABCG8
- Protein
- p.Leu336=
- Coding
- c.1006T>C
- MANE Select
- NM_022437
- dbSNP
- rs375507330
- Type
- single nucleotide variant
- Location
- chr2:43872017 (GRCh38)
- Gene constraint
- LOEUF 1.329 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
- Structure
- AlphaFold pLDDT 80.94 · 8 PDB
- Residue 336
- an α-helix
Similar variants
- ABCG8 p.Leu336Ser Uncertain significance ★★ ⚠ same residue
- ABCG8 p.Arg121Ter Pathogenic ★★ same condition
- ABCG8 p.Arg405Cys Pathogenic/Likely pathogenic ★★ ⚠ same condition
- ABCG8 p.Gln271Ter Pathogenic/Likely pathogenic ★★ same condition
- ABCG8 p.Ala248Thr Uncertain significance ★★ ⚠ same condition
- ABCG8 p.Ala346Thr Uncertain significance ★★ ⚠ same condition
- ABCG8 p.Ala449Val Uncertain significance ★★ ⚠ same condition
- ABCG8 p.Ala450Thr 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/abcg8-p-leu336 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown