DEF6 p.Arg330=
c.990C>T · rs191948544 · VCV1601179
Benign
Single submitter
Classification
Benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
rare (popmax 0.253%, eas)
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 -2.1 | GERP -4.1 |
| Overall | ||
| CADD | 8.315 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.253%
East Asian · 111/43,930 alleles
Filtering AF
0.215%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.2%
Overall
0.00873%
139/1,592,534 alleles · rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| East Asiangrpmax | 0.253% | 396 |
| Middle Eastern | 0.0335% | 2,984 |
| Finnishnot grpmax-eligible | 0.0196% | 5,099 |
| Remaining individualsnot grpmax-eligible | 0.0146% | 6,828 |
| European (non-Finnish) | 0.000427% | 234,135 |
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.Arg330=
- Coding
- c.990C>T
- MANE Select
- NM_022047
- dbSNP
- rs191948544
- Type
- single nucleotide variant
- Location
- chr6:35318246 (GRCh38)
- Gene constraint
- LOEUF 0.61 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 78.91
- Residue 330
- 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.Arg330_Glu331insLysArgArg 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-arg330 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown