DEF6 p.Ala17=
c.51G>A · rs764418962 · VCV1538427
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.00508%, amr)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP -2.4 | GERP -3.6 |
| Overall | ||
| CADD | 8.156 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00508%
Admixed American · 3/59,024 alleles
Filtering AF
0.00135%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.000674%
Overall
0.000684%
11/1,607,550 alleles · very rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Admixed Americangrpmax | 0.00508% | 19,675 |
| South Asian | 0.00223% | 44,799 |
| Remaining individualsnot grpmax-eligible | 0.00161% | 62,278 |
| Finnishnot grpmax-eligible | 0.00158% | 63,118 |
| European (non-Finnish) | 0.00034% | 294,401 |
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.Ala17=
- Coding
- c.51G>A
- MANE Select
- NM_022047
- dbSNP
- rs764418962
- Type
- single nucleotide variant
- Location
- chr6:35297907 (GRCh38)
- Gene constraint
- LOEUF 0.61 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 78.91
Similar variants
- DEF6 p.Ala17Thr Uncertain significance ★ ⚠ same residue
- DEF6 p.Ala17Val Uncertain significance ★ ⚠ same residue
- 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
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-ala17 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown