DEF6 p.Gln591=
c.1773G>A · rs148307710 · VCV1591037
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.0196%, nfe)
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 0.35 | GERP -0.4, phastCons 0.42 |
| Overall | ||
| CADD | 4.008 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0196%
European (non-Finnish) · 231/1,179,992 alleles
Filtering AF
0.0175%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0167%
Overall
0.0147%
237/1,613,804 alleles · ultra-rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| European (non-Finnish)grpmax | 0.0196% | 5,108 |
| Remaining individualsnot grpmax-eligible | 0.0064% | 15,618 |
| African / African-American | 0.00267% | 37,433 |
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.Gln591=
- Coding
- c.1773G>A
- MANE Select
- NM_022047
- dbSNP
- rs148307710
- Type
- single nucleotide variant
- Location
- chr6:35321287 (GRCh38)
- Gene constraint
- LOEUF 0.61 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 78.91
- Residue 591
- a UniProt-annotated variant site (in imd87; protein not detected in homozygous patient t cells or when the mutant is expressed in a heterologous system); the 'disordered' region
Similar variants
- DEF6 p.Gln591Arg 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
- DEF6 p.Arg349Leu 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-gln591 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown