BTBD3 p.Ala303=
c.909G>A · rs35364034 · VCV1226908
Benign
Multiple submitters
Classification
Benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Common
common (popmax 25.3%, eas) — too common for a highly-penetrant pathogenic allele
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 -1.1 | GERP -4 |
| Overall | ||
| CADD | 7.47 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
25.3%
East Asian · 11,370/44,878 alleles
Filtering AF
24.9%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 24.8%
Overall
5.7%
91,931/1,614,150 alleles · common
| Ancestry group | Frequency | 1 in |
|---|---|---|
| East Asiangrpmax | 25.3% | 4 |
| South Asian | 11.1% | 9 |
| Admixed American | 7.72% | 13 |
| Middle Eastern | 7.27% | 14 |
| Remaining individualsnot grpmax-eligible | 6.36% | 16 |
| Ashkenazi Jewishnot grpmax-eligible | 4.96% | 20 |
| European (non-Finnish) | 4.72% | 21 |
| African / African-American | 3.81% | 26 |
| Finnishnot grpmax-eligible | 2.11% | 47 |
| Amishnot grpmax-eligible | 1.43% | 70 |
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
- BTBD3
- Protein
- p.Ala303=
- Coding
- c.909G>A
- MANE Select
- NM_014962
- dbSNP
- rs35364034
- Type
- single nucleotide variant
- Location
- chr20:11923006 (GRCh38)
- Gene constraint
- LOEUF 0.527 · pLI 0.95 (gnomAD)
- Structure
- AlphaFold pLDDT 83.60
Similar variants
- BTBD3 p.Ala303Val Uncertain significance ★ ⚠ same residue
- BTBD3 p.Ala176Thr Uncertain significance ★ ⚠ same type
- BTBD3 p.Ala189Thr Uncertain significance ★ ⚠ same type
- BTBD3 p.Ala200Ser Uncertain significance ★ same type
- BTBD3 p.Ala73Asp Uncertain significance ★ ⚠ same type
- BTBD3 p.Ala96Val Uncertain significance ★ ⚠ same type
- BTBD3 p.Arg374Leu Uncertain significance ★ ⚠ same type
- BTBD3 p.Arg377Cys 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/btbd3-p-ala303 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown