BIN3 p.Ser229=
c.687C>T · VCV4209212
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
rare (popmax 0.107%, eas)
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 -14 | GERP -3.2 |
| Overall | ||
| CADD | 0.127 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.107%
East Asian · 48/44,888 alleles
Filtering AF
0.0829%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0743%
Overall
0.0118%
190/1,613,946 alleles · rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| East Asiangrpmax | 0.107% | 935 |
| Middle Eastern | 0.0165% | 6,058 |
| Admixed American | 0.015% | 6,669 |
| South Asian | 0.00988% | 10,121 |
| European (non-Finnish) | 0.00983% | 10,172 |
| Remaining individualsnot grpmax-eligible | 0.0096% | 10,415 |
| African / African-American | 0.00133% | 75,064 |
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
- BIN3
- Protein
- p.Ser229=
- Coding
- c.687C>T
- MANE Select
- NM_018688
- Type
- single nucleotide variant
- Location
- chr8:22621497 (GRCh38)
- Gene constraint
- LOEUF 1.45 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 92.83
- Residue 229
- the bar domain; the 'disordered' region
Similar variants
- BIN3 p.Ser229Phe Uncertain significance ★ ⚠ same residue
- BIN3 p.Ser229Tyr Uncertain significance ★ ⚠ same residue
- BIN3 c.297+5C>T Benign ★★ same type
- BIN3 p.Ala131Pro Uncertain significance ★ ⚠ same type
- BIN3 p.Arg128Gln Uncertain significance ★ ⚠ same type
- BIN3 p.Arg128Trp Uncertain significance ★ ⚠ same type
- BIN3 p.Arg136Gly Uncertain significance ★ ⚠ same type
- BIN3 p.Arg166Gln 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/bin3-p-ser229 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown