BFSP1 p.Leu225=
c.675G>A · rs140834233 · VCV541142
Benign
Multiple submitters
Classification
Benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
low-frequency (popmax 3.98%, eas)
Conditions
1
cataract 33
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 1.5 | GERP 1.8, phastCons 1 |
| Overall | ||
| CADD | 12.59 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
3.98%
East Asian · 1,761/44,258 alleles
Filtering AF
3.82%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 3.76%
Overall
0.153%
2,459/1,604,808 alleles · low-frequency
| Ancestry group | Frequency | 1 in |
|---|---|---|
| East Asiangrpmax | 3.98% | 25 |
| South Asian | 0.437% | 229 |
| Middle Eastern | 0.348% | 288 |
| Remaining individualsnot grpmax-eligible | 0.158% | 634 |
| Admixed American | 0.034% | 2,938 |
| Ashkenazi Jewishnot grpmax-eligible | 0.017% | 5,888 |
| African / African-American | 0.0134% | 7,478 |
| European (non-Finnish) | 0.0132% | 7,590 |
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
- BFSP1
- Protein
- p.Leu225=
- Coding
- c.675G>A
- MANE Select
- NM_001195
- dbSNP
- rs140834233
- Type
- single nucleotide variant
- Location
- chr20:17508949 (GRCh38)
- Gene constraint
- LOEUF 1.371 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 64.66
- Residue 225
- the if rod domain; the 'coil 2' region
Similar variants
- BFSP1 p.Ala643Thr Uncertain significance ★★ ⚠ same condition
- BFSP1 p.Arg560Cys Uncertain significance ★★ ⚠ same condition
- BFSP1 p.Arg69Trp Uncertain significance ★★ ⚠ same condition
- BFSP1 p.Asp19Asn Uncertain significance ★★ ⚠ same condition
- BFSP1 p.Gln294Arg Uncertain significance ★★ ⚠ same condition
- BFSP1 p.Gly46Trp Uncertain significance ★★ ⚠ same condition
- BFSP1 p.Ile271Thr Uncertain significance ★★ ⚠ same condition
- BFSP1 p.Leu68Phe Uncertain significance ★★ ⚠ 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/bfsp1-p-leu225 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown