BTNL8 p.His286=
c.858C>T · VCV3826038
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
rare (popmax 0.127%, afr)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| REVEL | 0.01 | strongly benign-leaning |
|---|---|---|
| Splicing | ||
| SpliceAI | <0.2 | all four deltas below 0.2 · C>G here scores Δ0.35 · evaluated, not missing |
| Constraint at this position | ||
| Conservation | phyloP -3.4 | GERP -2.1 |
| Overall | ||
| CADD | 5.082 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.127%
African / African-American · 91/71,526 alleles
Filtering AF
0.106%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0982%
Overall
0.00842%
123/1,460,646 alleles · rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 0.127% | 786 |
| Middle Eastern | 0.0351% | 2,847 |
| Admixed American | 0.0113% | 8,815 |
| Remaining individualsnot grpmax-eligible | 0.00523% | 19,107 |
| European (non-Finnish) | 0.00189% | 52,909 |
| South Asian | 0.00112% | 89,188 |
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
- BTNL8
- Protein
- p.His286=
- Coding
- c.858C>T
- MANE Select
- NM_001040462
- Type
- single nucleotide variant
- Location
- chr5:180949261 (GRCh38)
- Gene constraint
- LOEUF 0.88 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 86.68 · 1 PDB
- Residue 286
- the b30.2/spry domain
Similar variants
- BTNL8 p.Ala267= Likely benign ★★ same type
- BTNL8 p.Ala211Val Uncertain significance ★ ⚠ same type
- BTNL8 p.Ala283Thr Uncertain significance ★ ⚠ same type
- BTNL8 p.Ala475Thr Uncertain significance ★ ⚠ same type
- BTNL8 p.Ala50Pro Uncertain significance ★ ⚠ same type
- BTNL8 p.Ala93Val Uncertain significance ★ ⚠ same type
- BTNL8 p.Arg162Gly Uncertain significance ★ ⚠ same type
- BTNL8 p.Arg162Trp 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/btnl8-p-his286 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown