BBC3 p.Ser75Phe
c.224C>T · rs374925052 · VCV2508533
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.0261%, eas)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| REVEL | 0.248 | benign-leaning |
|---|---|---|
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
| Constraint at this position | ||
| Conservation | phyloP 7.9 | GERP 3.7, phastCons 1 |
| Regional constraint | o/e 0.83 | unconstrained · MANE · 6,626 bp · p 0.0062 · regional, not allelic |
| Overall | ||
| CADD | 23.3 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0261%
East Asian · 5/19,168 alleles
Filtering AF
0.0103%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0066%
Overall
0.00173%
19/1,098,208 alleles · ultra-rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| East Asiangrpmax | 0.0261% | 3,834 |
| Remaining individualsnot grpmax-eligible | 0.0241% | 4,147 |
| European (non-Finnish) | 0.000551% | 181,336 |
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
- BBC3
- Protein
- p.Ser75Phe
- Coding
- c.224C>T
- MANE Select
- NM_014417
- dbSNP
- rs374925052
- Type
- single nucleotide variant
- Location
- chr19:47228208 (GRCh38)
- Gene constraint
- LOEUF 1.293 · pLI 0.05 (gnomAD)
- Structure
- AlphaFold pLDDT 47.60 · 13 PDB
- Residue 75
- the 'disordered' region
Similar variants
- BBC3 c.*23C>T Benign/Likely benign ★★ same type
- BBC3 c.-3G>A Uncertain significance ★ ⚠ same type
- BBC3 c.*16C>T Uncertain significance ★ ⚠ same type
- BBC3 c.*46C>T Uncertain significance ★ ⚠ same type
- BBC3 c.*57C>T Uncertain significance ★ ⚠ same type
- BBC3 c.*64C>G Uncertain significance ★ ⚠ same type
- BBC3 c.*76C>G Uncertain significance ★ ⚠ same type
- BBC3 c.*79G>T 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/bbc3-p-ser75phe (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown