DEF6 p.Phe119=
c.357C>T · rs150977102 · VCV1169523
Benign/Likely benign
Multiple submitters
Classification
Benign/Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 3 submitters
gnomAD v4.1
Rare
rare (popmax 0.349%, sas)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| REVEL | 0.142 | moderately benign-leaning |
|---|---|---|
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
| Constraint at this position | ||
| Conservation | phyloP 2.5 | GERP 0.93, phastCons 1 |
| Overall | ||
| CADD | 12.1 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.349%
South Asian · 318/91,088 alleles
Filtering AF
0.318%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.305%
Overall
0.114%
1,834/1,614,162 alleles · rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| South Asiangrpmax | 0.349% | 286 |
| Middle Eastern | 0.297% | 337 |
| European (non-Finnish) | 0.116% | 861 |
| Remaining individualsnot grpmax-eligible | 0.107% | 933 |
| Admixed American | 0.07% | 1,429 |
| African / African-American | 0.016% | 6,251 |
| Finnishnot grpmax-eligible | 0.00937% | 10,673 |
| Ashkenazi Jewishnot grpmax-eligible | 0.00338% | 29,608 |
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.Phe119=
- Coding
- c.357C>T
- MANE Select
- NM_022047
- dbSNP
- rs150977102
- Type
- single nucleotide variant
- Location
- chr6:35310578 (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-phe119 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown