DPYS p.Arg355=
c.1063C>A · VCV4901390
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.00669%, eas)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation/SpliceAI carries the signal. | ||
| Splicing | ||
| SpliceAI | Δ0.30 | donor loss, 29 bp away · masked 0 · deltas |
|---|---|---|
| Pangolin | Δ0.28 | loss · gain 0.12 · agrees with SpliceAI · independent |
| Constraint at this position | ||
| Conservation | phyloP 5.8 | GERP 0.056, phastCons 1 |
| Overall | ||
| CADD | 9.064 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00669%
East Asian · 3/44,874 alleles
Filtering AF
0.00177%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.000891%
Overall
0.000186%
3/1,614,170 alleles · very rare
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.Arg355=
- Coding
- c.1063C>A
- MANE Select
- NM_001385
- Type
- single nucleotide variant
- Location
- chr8:104428009 (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 355
- an α-helix
Similar variants
- DPYS p.Arg355Gln Likely pathogenic ★ same residue
- DPYS p.Arg355Trp Uncertain significance ★ ⚠ 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
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-arg355 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown