Is DPYD p.Ser201Arg (c.601A>C) pathogenic?

DPYD p.Ser201Arg (c.601A>C) is classified Likely pathogenic in DPYD (ClinVar, Multiple submitters, 4 submitters; last evaluated 2026-02-04). AlphaMissense: likely pathogenic (0.9982); Very rare (popmax 0.0078%, nfe); Associated with dihydropyrimidine dehydrogenase deficiency.

What condition is associated with DPYD p.Ser201Arg (c.601A>C)?

DPYD p.Ser201Arg (c.601A>C) is associated with dihydropyrimidine dehydrogenase deficiency (ClinVar).

How common is DPYD p.Ser201Arg (c.601A>C) in the general population?

DPYD p.Ser201Arg (c.601A>C) is very rare (popmax 0.0078%, nfe) (gnomAD).

How is Dihydropyrimidine dehydrogenase deficiency inherited?

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

What do computational predictors say about DPYD p.Ser201Arg (c.601A>C)?

AlphaMissense predicts likely pathogenic (score 0.9982) — an in-silico prediction, not a clinical call.

DPYD p.Ser201Arg

c.601A>C · rs72549308 · VCV2674903

Likely pathogenic Multiple submitters

Classification

Likely pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

AlphaMissense

likely pathogenic

0.9982 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.0078%, nfe)

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

dihydropyrimidine dehydrogenase deficiency

Computational evidence

Protein change
AlphaMissense	0.9982	likely pathogenic ✓ concordant with ClinVar · top 1% in DPYD
REVEL	0.895	moderately pathogenic-leaning
SaProt	LLR -16.17	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.9	GERP 1.7, phastCons 1
Regional constraint	o/e 1.04	unconstrained · MANE · 842 kb · p 0.18 · regional, not allelic
Overall
CADD	28.1	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0078% European (non-Finnish) · 92/1,179,730 alleles

Filtering AF 0.00648% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.006%

Overall 0.00589% 95/1,613,598 alleles · very rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.0078%	12,823
African / African-American	0.00267%	37,440
Remaining individualsnot grpmax-eligible	0.0016%	62,474

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.Ser201Arg
Coding: c.601A>C
MANE Select: NM_000110
dbSNP: rs72549308
Type: single nucleotide variant
Location: chr1:97699430 (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 c.1340-2A>C Likely pathogenic ★★ same condition
DPYD c.1905+1G>C Pathogenic/Likely pathogenic ★★ same condition
DPYD c.233+1G>T Likely pathogenic ★★ same condition
DPYD c.2622+1G>A Likely pathogenic ★★ same condition
DPYD c.2767-1G>A Likely pathogenic ★★ same condition
DPYD c.680+1G>T Likely pathogenic ★★ same condition
DPYD p.Arg21Ter Pathogenic/Likely pathogenic ★★ same condition
DPYD p.Arg561Ter Pathogenic/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-ser201arg (accessed [today's date]).

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