Is DPYS p.Ala450= (c.1350C>T) pathogenic?

DPYS p.Ala450= (c.1350C>T) is classified Benign in DPYS (ClinVar, Multiple submitters, 3 submitters; last evaluated 2026-01-15). Low-frequency (popmax 2.51%, afr); Associated with dihydropyrimidinuria.

What condition is associated with DPYS p.Ala450= (c.1350C>T)?

DPYS p.Ala450= (c.1350C>T) is associated with dihydropyrimidinuria (ClinVar).

How common is DPYS p.Ala450= (c.1350C>T) in the general population?

DPYS p.Ala450= (c.1350C>T) is low-frequency (popmax 2.51%, afr) (gnomAD).

How is Dihydropyrimidinuria inherited?

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

DPYS p.Ala450=

c.1350C>T · rs75490773 · VCV361448

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

gnomAD v4.1

Rare

low-frequency (popmax 2.51%, afr)

Conditions

dihydropyrimidinuria

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 -0.64	GERP -4.1
Overall
CADD	7.136	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 2.51% African / African-American · 1,882/75,026 alleles

Filtering AF 2.41% ClinGen BA1/BS1 input FAF95, joint · FAF99 2.38%

Overall 0.139% 2,237/1,614,146 alleles · low-frequency

Ancestry group	Frequency	1 in
African / African-Americangrpmax	2.51%	40
Admixed American	0.172%	583
Remaining individualsnot grpmax-eligible	0.17%	590
Middle Eastern	0.066%	1,516
South Asian	0.0472%	2,118
East Asian	0.0178%	5,610
European (non-Finnish)	0.00754%	13,259
Ashkenazi Jewishnot grpmax-eligible	0.00338%	29,606
Finnishnot grpmax-eligible	0.00156%	64,034

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.Ala450=
Coding: c.1350C>T
MANE Select: NM_001385
dbSNP: rs75490773
Type: single nucleotide variant
Location: chr8:104392877 (GRCh38)
Gene constraint: LOEUF 1.029 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 96.00 · 1 PDB

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

Disease context

dihydropyrimidinuria — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Dihydropyrimidinuria (Orphanet):

Inheritance: Autosomal recessive
Onset: Childhood, Infancy
Prevalence: <1 / 1 000 000 (Worldwide)

Similar variants

DPYS p.Arg302Gln Likely pathogenic ★★ same condition
DPYS p.Arg302Ter Pathogenic/Likely pathogenic ★★ same condition
DPYS p.Arg465Ter Pathogenic ★★ same condition
DPYS p.Arg475Ter Pathogenic/Likely pathogenic ★★ same condition
DPYS p.Arg490Cys Pathogenic/Likely pathogenic ★★ same condition
DPYS p.Arg490His Pathogenic/Likely pathogenic ★★ same condition
DPYS p.Gln190Ter Pathogenic ★★ same condition
DPYS p.Gln334Arg 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/dpys-p-ala450 (accessed [today's date]).

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