BEST1 p.Phe17Ser
c.50T>C · VCV3721038
Pathogenic/Likely pathogenic
Multiple submitters
Classification
Pathogenic/Likely pathogenic
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
AlphaMissense
likely pathogenic
0.9804 · ACMG-weighted
gnomAD v4.1
Absent
absent from gnomAD v4.1
Missense predictors
3/3 damaging
AlphaMissense, REVEL, SaProt
Conditions
1
BEST1-related disorder
Computational evidence
| Protein change | ||
| AlphaMissense | 0.9804 | likely pathogenic ✓ concordant with ClinVar · top 8% in BEST1 |
|---|---|---|
| REVEL | 0.971 | strongly pathogenic-leaning |
| SaProt | LLR -14.94 | damaging |
| ⇒ AlphaMissense, REVEL and SaProt all call this damaging. | ||
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
| Constraint at this position | ||
| Conservation | phyloP 2.7 | GERP 1.4, phastCons 1 |
| Regional constraint | o/e 0.91 | unconstrained · MANE · 12 kb · p 0.011 · regional, not allelic |
| Overall | ||
| CADD | 27.7 | PHRED · no single calibrated threshold — expert panels disagree |
AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.
Population frequency
gnomAD v4.1 · exomes + genomes
Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.
Variant & gene context
- Gene
- BEST1
- Protein
- p.Phe17Ser
- Coding
- c.50T>C
- MANE Select
- NM_004183
- Type
- single nucleotide variant
- Location
- chr11:61951856 (GRCh38)
- Gene constraint
- LOEUF 1.28 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 72.46 · 19 PDB
- Residue 17
- an α-helix; a UniProt-annotated variant site (in vmd2)
Similar variants
- BEST1 p.Phe17Ile Likely pathogenic ★ same residue
- BEST1 p.Phe17Tyr Likely pathogenic ★ same residue
- BEST1 p.Phe17Leu Uncertain significance ★ ⚠ same residue
- BEST1 p.Phe17Val Uncertain significance ★ same residue
- BEST1 c.636+1G>A Pathogenic ★★ same condition
- BEST1 p.Ala10Val Pathogenic ★★ same condition
- BEST1 p.Arg105Ser Pathogenic/Likely pathogenic ★★ same condition
- BEST1 p.Arg130Ser Pathogenic/Likely pathogenic ★★ same condition
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-phe17ser (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown