BEST1 p.Ala321=
c.963T>C · rs765333391 · VCV2180873
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
ultra-rare (popmax 0.0657%, mid)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| REVEL | 0.257 | benign-leaning |
|---|---|---|
| Splicing | ||
| SpliceAI | <0.2 | all four deltas below 0.2 · T>A here scores Δ0.73 · evaluated, not missing |
| Constraint at this position | ||
| Conservation | phyloP -3.2 | GERP -2.2 |
| Overall | ||
| CADD | 5.847 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0657%
Middle Eastern · 4/6,084 alleles
Filtering AF
0.0224%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0135%
Overall
0.00112%
18/1,613,712 alleles · ultra-rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Middle Easterngrpmax | 0.0657% | 1,521 |
| Remaining individualsnot grpmax-eligible | 0.0064% | 15,619 |
| Admixed American | 0.005% | 19,985 |
| Finnishnot grpmax-eligible | 0.00156% | 64,022 |
| African / African-American | 0.00133% | 74,918 |
| European (non-Finnish) | 0.000424% | 235,983 |
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
- BEST1
- Protein
- p.Ala321=
- Coding
- c.963T>C
- MANE Select
- NM_004183
- dbSNP
- rs765333391
- Type
- single nucleotide variant
- Location
- chr11:61959906 (GRCh38)
- Gene constraint
- LOEUF 1.28 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 72.46 · 19 PDB
- Residue 321
- an α-helix
Similar variants
- BEST1 c.1100+1G>C Pathogenic/Likely pathogenic ★★ same type
- BEST1 c.1101-1G>C Likely pathogenic ★★ same type
- BEST1 c.636+1G>A Pathogenic ★★ same type
- BEST1 c.867+97G>A Pathogenic/Likely pathogenic ★★ same type
- BEST1 p.Ala10Thr Pathogenic ★★ same type
- BEST1 p.Ala10Val Pathogenic ★★ same type
- BEST1 p.Ala195Val Pathogenic/Likely pathogenic ★★ ⚠ same type
- BEST1 p.Ala243Thr Pathogenic ★★ 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/best1-p-ala321 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown