DEF6 p.Pro48=
c.144C>T · VCV3695790
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.0233%, amr)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Splicing | ||
| SpliceAI | <0.2 | no splice effect predicted · four deltas, not one · how we know |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP -20 | GERP -3.8 |
| Overall | ||
| CADD | 2.795 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0233%
Admixed American · 14/59,986 alleles
Filtering AF
0.0141%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0112%
Overall
0.00112%
18/1,613,916 alleles · ultra-rare
exomes 9/1,461,874 · genomes 9/152,042 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Admixed Americangrpmax | 0.0233% | 4,285 |
| Remaining individualsnot grpmax-eligible | 0.0016% | 62,484 |
| South Asian | 0.0011% | 91,074 |
| European (non-Finnish) | 0.000169% | 590,009 |
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
- DEF6
- Protein
- p.Pro48=
- Coding
- c.144C>T
- MANE Select
- NM_022047
- Type
- single nucleotide variant
- Location
- chr6:35309717 (GRCh38)
- Gene constraint
- LOEUF 0.61 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 78.91
Similar variants
- DEF6 p.Ala395Glu Uncertain significance ★★ ⚠ same type
- DEF6 p.Ala617Val Uncertain significance ★★ ⚠ same type
- DEF6 p.Arg104Pro Uncertain significance ★★ ⚠ same type
- DEF6 p.Arg104Trp Uncertain significance ★★ ⚠ same type
- DEF6 p.Arg192Cys Uncertain significance ★★ ⚠ same type
- DEF6 p.Arg195Gln Uncertain significance ★★ ⚠ same type
- DEF6 p.Arg349Leu Uncertain significance ★★ ⚠ same type
- DEF6 p.Arg4Cys 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/def6-p-pro48 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown