DPYS p.Leu7=
c.21C>T · rs755857356 · VCV1901068
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
rare (popmax 0.102%, mid)
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 -0.025 | GERP -3.3, phastCons 0.44 |
| Overall | ||
| CADD | 3.765 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.102%
Middle Eastern · 5/4,884 alleles
Filtering AF
0.0403%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0261%
Overall
0.00185%
25/1,352,332 alleles · rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Middle Easterngrpmax | 0.102% | 977 |
| South Asian | 0.0211% | 4,747 |
| Remaining individualsnot grpmax-eligible | 0.00342% | 29,249 |
| East Asian | 0.00265% | 37,736 |
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
- DPYS
- Protein
- p.Leu7=
- Coding
- c.21C>T
- MANE Select
- NM_001385
- dbSNP
- rs755857356
- Type
- single nucleotide variant
- Location
- chr8:104466900 (GRCh38)
- Gene constraint
- LOEUF 1.029 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
- Structure
- AlphaFold pLDDT 96.00 · 1 PDB
- Residue 7
- a β-strand
Similar variants
- DPYS p.Leu7Val Likely benign ★★ same residue
- DPYS c.424-1G>A Pathogenic/Likely pathogenic ★★ same type
- DPYS p.Arg302Gln Likely pathogenic ★★ same type
- DPYS p.Arg302Ter Pathogenic/Likely pathogenic ★★ same type
- DPYS p.Arg465Ter Pathogenic ★★ same type
- DPYS p.Arg475Ter Pathogenic/Likely pathogenic ★★ same type
- DPYS p.Arg490Cys Pathogenic/Likely pathogenic ★★ same type
- DPYS p.Arg490His Pathogenic/Likely pathogenic ★★ 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/dpys-p-leu7 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown