DPYD c.321+15A>C
Conflicting classifications of pathogenicity
Conflicting submitters
Classification
Conflicting classifications of pathogenicity
ClinVar
Review
Conflicting submitters ★☆☆☆
ClinVar · 3 submitters
gnomAD v4.1
Rare
ultra-rare (popmax 0.083%, mid)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Splicing | ||
| Splice region | donor +15 | near-intronic (+15 nt from the splice site) |
|---|---|---|
| SpliceAI | — | not assessed · no allele here is in the release |
| Constraint at this position | ||
| Conservation | phyloP 0.52 | GERP -1 |
| Non-coding constraint | Z -1.53 | 1 kb window · o/e 1.12 · regional · uncalibrated |
| Overall | ||
| CADD | 11.54 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.083%
Middle Eastern · 5/6,024 alleles
Filtering AF
0.04%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0359%
Overall
0.00979%
156/1,593,848 alleles · ultra-rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Middle Easterngrpmax | 0.083% | 1,205 |
| South Asian | 0.0518% | 1,929 |
| Remaining individualsnot grpmax-eligible | 0.013% | 7,720 |
| European (non-Finnish) | 0.00809% | 12,364 |
| African / African-American | 0.00268% | 37,255 |
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
- DPYD
- Coding
- c.321+15A>C
- MANE Select
- NM_000110
- dbSNP
- rs370363977
- Type
- single nucleotide variant
- Location
- chr1:97740377 (GRCh38)
- Gene constraint
- LOEUF 1.09 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
- Structure
- AlphaFold pLDDT 96.23
Similar variants
- DPYD c.1340-2A>C Likely pathogenic ★★ same type
- DPYD c.1905+1G>C Pathogenic/Likely pathogenic ★★ same type
- DPYD c.233+1G>T Likely pathogenic ★★ same type
- DPYD c.2622+1G>A Likely pathogenic ★★ same type
- DPYD c.2767-1G>A Likely pathogenic ★★ same type
- DPYD c.680+1G>T Likely pathogenic ★★ same type
- DPYD p.Arg21Ter Pathogenic/Likely pathogenic ★★ same type
- DPYD p.Arg561Ter 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/dpyd-c-321-plus-15a-c (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown