DPYD p.Leu741=
c.2223G>C · rs1397691452 · VCV2638936
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.000509%, nfe)
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 0.29 | GERP 1.7, phastCons 0.98 |
| Overall | ||
| CADD | 4.442 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.000509%
European (non-Finnish) · 6/1,178,954 alleles
Filtering AF
0.000183%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00012%
Overall
0.000372%
6/1,612,376 alleles · very rare
exomes 5/1,460,464 · genomes 1/151,912 · joint denominator
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
- Protein
- p.Leu741=
- Coding
- c.2223G>C
- MANE Select
- NM_000110
- dbSNP
- rs1397691452
- Type
- single nucleotide variant
- Location
- chr1:97305335 (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-p-leu741 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown