EBF3 p.Ser466=
c.1398C>T · VCV4909934
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.00169%, amr)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| REVEL | 0.185 | benign-leaning |
|---|---|---|
| Splicing | ||
| SpliceAI | <0.2 | all four deltas below 0.2 · G>C here scores Δ0.20 · evaluated, not missing |
| Constraint at this position | ||
| Conservation | phyloP 6.5 | GERP 1.9, phastCons 1 |
| Overall | ||
| CADD | 13.56 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00169%
Admixed American · 1/59,220 alleles
Filtering AF
0.000764%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.000606%
Overall
0.00106%
17/1,608,174 alleles · very rare
exomes 17/1,460,270 · genomes 0/147,904 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Admixed Americangrpmax | 0.00169% | 59,220 |
| Finnishnot grpmax-eligible | 0.00161% | 62,208 |
| European (non-Finnish) | 0.00127% | 78,568 |
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
- EBF3
- Protein
- p.Ser466=
- Coding
- c.1398C>T
- MANE Select
- NM_001375380
- Type
- single nucleotide variant
- Location
- chr10:129841007 (GRCh38)
- Gene constraint
- LOEUF 0.353 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
- Structure
- AlphaFold pLDDT 71.89 · 2 PDB
- Residue 466
- the 'disordered' region
Similar variants
- EBF3 c.486-1G>A Pathogenic ★★ same type
- EBF3 c.555-2A>G Likely pathogenic ★★ same type
- EBF3 p.Arg152Gly Pathogenic ★★ same type
- EBF3 p.Arg163Gln Pathogenic ★★ same type
- EBF3 p.Arg163Leu Pathogenic ★★ same type
- EBF3 p.Arg163Trp Pathogenic/Likely pathogenic ★★ same type
- EBF3 p.Arg206Ter Pathogenic ★★ same type
- EBF3 p.Arg209Gln Pathogenic/Likely 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/ebf3-p-ser466 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown