ABCG8 p.Ser256=
c.768C>T · rs1558811634 · VCV596961
Conflicting classifications of pathogenicity
Conflicting submitters
Classification
Conflicting classifications of pathogenicity
ClinVar
Review
Conflicting submitters ★☆☆☆
ClinVar · 3 submitters
gnomAD v4.1
Rare
very rare (popmax 0.000169%, nfe)
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 -0.39 | GERP -0.014, phastCons 0.013 |
| Overall | ||
| CADD | 6.465 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.000169%
European (non-Finnish) · 2/1,180,032 alleles
Filtering AF
2.8e-05%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 1.1e-05%
Overall
0.000124%
2/1,614,212 alleles · very rare
exomes 2/1,461,892 · genomes 0/152,320 · joint denominator
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.Ser256=
- Coding
- c.768C>T
- MANE Select
- NM_022437
- dbSNP
- rs1558811634
- Type
- single nucleotide variant
- Location
- chr2:43852672 (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 256
- the abc transporter domain; an α-helix
Similar variants
- 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
- ABCG8 p.Ala506Ser 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-ser256 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown