Is DPYD p.Leu5fs (c.12dup) pathogenic?

DPYD p.Leu5fs (c.12dup) is classified Pathogenic in DPYD (ClinVar, Single submitter, 1 submitter; last evaluated 2025-09-30). Associated with dihydropyrimidine dehydrogenase deficiency.

What condition is associated with DPYD p.Leu5fs (c.12dup)?

DPYD p.Leu5fs (c.12dup) is associated with dihydropyrimidine dehydrogenase deficiency (ClinVar).

How is Dihydropyrimidine dehydrogenase deficiency inherited?

Typically Autosomal recessive (Orphanet). A genetic counselor can assess individual risk for a family.

DPYD p.Leu5fs

c.12dup · VCV4536140

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

Conditions

dihydropyrimidine dehydrogenase deficiency

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function
NMD	predicted	premature termination codon in exon 1 of 23
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 11	GERP 1.7, phastCons 1

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Variant & gene context

Gene: DPYD
Protein: p.Leu5fs
Coding: c.12dup
MANE Select: NM_000110
Type: Duplication
Location: chr1:97920910 (GRCh38)
Gene constraint: LOEUF 1.09 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 96.23

Full DPYD gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

dihydropyrimidine dehydrogenase deficiency — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Dihydropyrimidine dehydrogenase deficiency (Orphanet):

Inheritance: Autosomal recessive
Onset: All ages

Similar variants

DPYD p.Leu461fs Pathogenic/Likely pathogenic ★★ same condition
DPYD c.1905+2dup Likely pathogenic ★ same condition
DPYD p.Arg332fs Likely pathogenic ★ same condition
DPYD p.Asn736fs Pathogenic ★ same condition
DPYD p.Asp346Ter Likely pathogenic ★ same condition
DPYD p.Ile454fs Likely pathogenic ★ same condition
DPYD p.Ile591fs Likely pathogenic ★ same condition
DPYD p.Leu572fs Likely pathogenic ★ same condition

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-leu5fs (accessed [today's date]).

Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown