DEF6 p.Tyr13=
c.39C>T · rs1181650801 · VCV2992437
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.00339%, amr)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Splicing | ||
| SpliceAI | <0.2 | all four deltas below 0.2 · C>A here scores Δ0.61 · evaluated, not missing |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP -5.7 | GERP -3.6 |
| Overall | ||
| CADD | 11.83 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00339%
Admixed American · 2/59,064 alleles
Filtering AF
0.000562%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00021%
Overall
0.000684%
11/1,607,644 alleles · very rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Admixed Americangrpmax | 0.00339% | 29,532 |
| East Asian | 0.00224% | 44,670 |
| Finnishnot grpmax-eligible | 0.00158% | 63,096 |
| African / African-American | 0.00133% | 74,912 |
| South Asian | 0.00112% | 89,614 |
| European (non-Finnish) | 0.000425% | 235,529 |
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.Tyr13=
- Coding
- c.39C>T
- MANE Select
- NM_022047
- dbSNP
- rs1181650801
- Type
- single nucleotide variant
- Location
- chr6:35297895 (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-tyr13 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown