BTNL8 p.Pro299=
c.897G>A · VCV3826040
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.025%, afr)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| REVEL | 0.011 | strongly benign-leaning |
|---|---|---|
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
| Constraint at this position | ||
| Conservation | phyloP -3.6 | GERP -3.3 |
| Overall | ||
| CADD | 2.923 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.025%
African / African-American · 18/72,096 alleles
Filtering AF
0.0161%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0133%
Overall
0.0024%
35/1,460,146 alleles · ultra-rare
exomes 23/1,324,880 · genomes 12/135,266 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 0.025% | 4,005 |
| Admixed American | 0.00377% | 26,547 |
| Remaining individualsnot grpmax-eligible | 0.00175% | 57,186 |
| European (non-Finnish) | 0.00132% | 75,569 |
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.Pro299=
- Coding
- c.897G>A
- MANE Select
- NM_001040462
- Type
- single nucleotide variant
- Location
- chr5:180949938 (GRCh38)
- Gene constraint
- LOEUF 0.88 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 86.68 · 1 PDB
- Residue 299
- 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-pro299 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown