Is DPYS p.Phe72= (c.216C>T) pathogenic?

DPYS p.Phe72= (c.216C>T) is classified Benign in DPYS (ClinVar, Multiple submitters, 4 submitters; last evaluated 2026-02-02). Common (popmax 32%, eas) — too common for a highly-penetrant pathogenic allele; Associated with dihydropyrimidinuria.

What condition is associated with DPYS p.Phe72= (c.216C>T)?

DPYS p.Phe72= (c.216C>T) is associated with dihydropyrimidinuria (ClinVar).

How is Dihydropyrimidinuria inherited?

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

DPYS p.Phe72=

Q: How common is DPYS p.Phe72= (c.216C>T) in the general population?

DPYS p.Phe72= (c.216C>T) is common (popmax 32%, eas) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.216C>T · rs2298840 · VCV100148

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

gnomAD v4.1

Common

common (popmax 32%, eas) — too common for a highly-penetrant pathogenic allele

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 2.1	GERP -3.9, phastCons 1
Overall
CADD	12.73	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 32% East Asian · 12,807/39,970 alleles

Filtering AF 31.6% ClinGen BA1/BS1 input FAF95, joint · FAF99 31.4%

Overall 18.8% 287,496/1,531,760 alleles · common

Ancestry group	Frequency	1 in
East Asiangrpmax	32%	3
African / African-American	25.7%	4
Middle Eastern	23.5%	4
Admixed American	20.6%	5
Remaining individualsnot grpmax-eligible	19.7%	5
Finnishnot grpmax-eligible	18.6%	5
Ashkenazi Jewishnot grpmax-eligible	18.3%	5
European (non-Finnish)	18.2%	6
Amishnot grpmax-eligible	16.9%	6
South Asian	13.1%	8

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.Phe72=
Coding: c.216C>T
MANE Select: NM_001385
dbSNP: rs2298840
Type: single nucleotide variant
Location: chr8:104466705 (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-phe72 (accessed [today's date]).

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