BEST1 p.Ala53=
c.159C>A · rs375873874 · VCV738245
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 3 submitters
gnomAD v4.1
Rare
ultra-rare (popmax 0.0226%, nfe)
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 -0.64 | GERP -4.5 |
| Overall | ||
| CADD | 7.688 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0226%
European (non-Finnish) · 267/1,180,042 alleles
Filtering AF
0.0204%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0195%
Overall
0.0168%
271/1,614,030 alleles · ultra-rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| European (non-Finnish)grpmax | 0.0226% | 4,420 |
| Remaining individualsnot grpmax-eligible | 0.0048% | 20,827 |
| African / African-American | 0.00133% | 74,924 |
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.Ala53=
- Coding
- c.159C>A
- MANE Select
- NM_004183
- dbSNP
- rs375873874
- Type
- single nucleotide variant
- Location
- chr11:61955113 (GRCh38)
- Gene constraint
- LOEUF 1.28 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 72.46 · 19 PDB
- Residue 53
- 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-ala53 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown