DEFB105B p.Cys67Phe
c.200G>T · rs751815246 · VCV3081294
Uncertain significance
Single submitter
Classification
Uncertain significance
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.00436%, nfe)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| REVEL | 0.498 | indeterminate |
|---|---|---|
| Splicing | ||
| SpliceAI | <0.2 | all four deltas below 0.2 · G>A here scores Δ0.26 · evaluated, not missing |
| Pangolin | Δ0.23 | gain · loss 0.00 · SpliceAI below 0.2 · independent |
| Constraint at this position | ||
| Conservation | phyloP 8.2 | GERP 5.1, phastCons 1 |
| Overall | ||
| CADD | 21.5 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00436%
European (non-Finnish) · 2/45,826 alleles
Filtering AF
0.000723%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.000271%
Overall
0.00252%
2/79,374 alleles · very rare
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
- DEFB105B
- Protein
- p.Cys67Phe
- Coding
- c.200G>T
- MANE Select
- NM_001040703
- dbSNP
- rs751815246
- Type
- single nucleotide variant
- Location
- chr8:7489514 (GRCh38)
- Structure
- AlphaFold pLDDT 72.22
- Residue 67
- a disulfide bond
Similar variants
- DEFB105B p.Cys67Tyr Uncertain significance ★ same residue
- DEFB105B p.Asp64Asn Uncertain significance ★ same type
- DEFB105B p.Leu72Val 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/defb105b-p-cys67phe (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown