ABCG8 p.Arg121=
c.361C>A · rs375005392 · VCV2628513
Uncertain significance
Single submitter
Classification
Uncertain significance
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.00267%, afr)
Conditions
1
ABCG8-related disorder
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 0.42 | GERP -1.9, phastCons 0.017 |
| Overall | ||
| CADD | 6.492 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00267%
African / African-American · 2/74,934 alleles
Filtering AF
0.000443%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.000166%
Overall
0.000124%
2/1,614,072 alleles · very rare
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.Arg121=
- Coding
- c.361C>A
- MANE Select
- NM_022437
- dbSNP
- rs375005392
- Type
- single nucleotide variant
- Location
- chr2:43851622 (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 121
- the abc transporter domain
Disease context
ABCG8-related disorder
Similar variants
- ABCG8 p.Arg121Ter Pathogenic ★★ same residue
- ABCG8 p.Arg121Gln Uncertain significance ★★ ⚠ same residue
- ABCG8 p.Arg121Gly Uncertain significance ★ ⚠ same residue
- ABCG8 p.Gly574Arg Pathogenic/Likely pathogenic ★★ same condition
- ABCG8 p.Trp361Ter Pathogenic/Likely pathogenic ★★ same condition
- ABCG8 p.Arg263Trp Uncertain significance ★★ ⚠ same condition
- ABCG8 p.Glu423Asp Uncertain significance ★★ ⚠ same condition
- ABCG8 c.1411+1G>A Likely pathogenic ★ 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-arg121 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown