Is DPYD p.Ser878Arg (c.2634T>G) pathogenic?

DPYD p.Ser878Arg (c.2634T>G) is classified Uncertain significance in DPYD (ClinVar, Single submitter, 1 submitter; last evaluated 2018-01-12). AlphaMissense: likely pathogenic (0.5815); Very rare (popmax 0.00501%, amr); Associated with dihydropyrimidine dehydrogenase deficiency.

What condition is associated with DPYD p.Ser878Arg (c.2634T>G)?

DPYD p.Ser878Arg (c.2634T>G) is associated with dihydropyrimidine dehydrogenase deficiency (ClinVar).

How common is DPYD p.Ser878Arg (c.2634T>G) in the general population?

DPYD p.Ser878Arg (c.2634T>G) is very rare (popmax 0.00501%, amr) (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.Ser878Arg (c.2634T>G)?

AlphaMissense predicts likely pathogenic (score 0.5815) — an in-silico prediction, not a clinical call.

DPYD p.Ser878Arg

c.2634T>G · rs919596571 · VCV874134

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.5815 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00501%, amr)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

dihydropyrimidine dehydrogenase deficiency

Computational evidence

Protein change
AlphaMissense	0.5815	likely pathogenic
REVEL	0.46	indeterminate
SaProt	LLR -5.05	tolerated
⇒ AlphaMissense calls this damaging; SaProt does not; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 1.4	GERP -0.43, phastCons 1
Regional constraint	o/e 1.04	unconstrained · MANE · 842 kb · p 0.18 · regional, not allelic
Overall
CADD	17.55	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 0.00501% Admixed American · 3/59,888 alleles

Filtering AF 0.00133% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000669%

Overall 0.000372% 6/1,612,804 alleles · very rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00501%	19,963
Remaining individualsnot grpmax-eligible	0.0016%	62,396
European (non-Finnish)	0.00017%	589,682

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.Ser878Arg
Coding: c.2634T>G
MANE Select: NM_000110
dbSNP: rs919596571
Type: single nucleotide variant
Location: chr1:97098621 (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.Ser878Gly Uncertain significance ★ ⚠ same residue
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

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-ser878arg (accessed [today's date]).

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