DGKE p.Pro7=
c.21G>A · rs758731271 · VCV1996411
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.0424%, mid)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Splicing | ||
| SpliceAI | <0.2 | no splice effect predicted · four deltas, not one · how we know |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP 0.31 | GERP 0.88, phastCons 0.99 |
| Overall | ||
| CADD | 10.56 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0424%
Middle Eastern · 2/4,714 alleles
Filtering AF
0.00745%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00309%
Overall
0.000312%
5/1,604,170 alleles · ultra-rare
exomes 4/1,451,946 · genomes 1/152,224 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Middle Easterngrpmax | 0.0424% | 2,357 |
| Remaining individualsnot grpmax-eligible | 0.00161% | 61,936 |
| European (non-Finnish) | 0.00017% | 588,042 |
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
- DGKE
- Protein
- p.Pro7=
- Coding
- c.21G>A
- MANE Select
- NM_003647
- dbSNP
- rs758731271
- Type
- single nucleotide variant
- Location
- chr17:56834816 (GRCh38)
- Gene constraint
- LOEUF 0.995 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
- Structure
- AlphaFold pLDDT 86.18
Similar variants
- DGKE p.Pro7Leu Uncertain significance ★ ⚠ same residue
- DGKE c.465-2A>G Pathogenic/Likely pathogenic ★★ same type
- DGKE c.889-1G>A Pathogenic ★★ same type
- DGKE p.Gln143Ter Pathogenic ★★ same type
- DGKE p.Trp322Ter Pathogenic ★★ same type
- DGKE p.Ala78Gly Uncertain significance ★★ ⚠ same type
- DGKE p.Arg227Cys Uncertain significance ★★ ⚠ same type
- DGKE p.Arg227His 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/dgke-p-pro7 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown