ABCB6 p.Arg276Gln
c.827G>A · rs200125320 · VCV1404017
Computational evidence
| Protein change | ||
| AlphaMissense | 0.8077 | likely pathogenic |
|---|---|---|
| REVEL | 0.804 | moderately pathogenic-leaning |
| SaProt | LLR -12.89 | damaging |
| ⇒ AlphaMissense, REVEL and SaProt all call this damaging. | ||
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
| Constraint at this position | ||
| Conservation | phyloP 7.6 | GERP 2.1, phastCons 1 |
| Regional constraint | o/e 0.96 | unconstrained · MANE · 8,732 bp · p 0.15 · regional, not allelic |
| Overall | ||
| CADD | 29.2 | PHRED · no single calibrated threshold — expert panels disagree |
ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — a triage signal, not a reclassification
AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.
Population frequency
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Finnishnot grpmax-eligible | 0.055% | 1,820 |
| European (non-Finnish)grpmax | 0.0213% | 4,699 |
| Remaining individualsnot grpmax-eligible | 0.013% | 7,679 |
| Ashkenazi Jewishnot grpmax-eligible | 0.00345% | 28,982 |
| South Asian | 0.00343% | 29,125 |
| Admixed American | 0.00182% | 54,934 |
| African / African-American | 0.00135% | 73,976 |
Finnish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.
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
- ABCB6
- Protein
- p.Arg276Gln
- Coding
- c.827G>A
- MANE Select
- NM_005689
- dbSNP
- rs200125320
- Type
- single nucleotide variant
- Location
- chr2:219216693 (GRCh38)
- Gene constraint
- LOEUF 0.984 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 83.17 · 16 PDB
- Residue 276
- the abc transmembrane type-1 domain; a UniProt-annotated variant site (may be a modifier of disease severity in porphyria patients; loss of expression); an α-helix
Similar variants
- ABCB6 p.Arg276Trp Benign/Likely benign ★★ same residue
- ABCB6 p.Arg276Pro Uncertain significance ★ ⚠ same residue
- ABCB6 p.Ala164Thr Uncertain significance ★★ ⚠ same type
- ABCB6 p.Ala57Thr Uncertain significance ★★ ⚠ same type
- ABCB6 p.Ala66Thr Uncertain significance ★★ ⚠ same type
- ABCB6 p.Ala681Thr Uncertain significance ★★ ⚠ same type
- ABCB6 p.Arg135Ser Uncertain significance ★★ ⚠ same type
- ABCB6 p.Arg439Cys 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/abcb6-p-arg276gln (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown