Is DPYD p.Pro3Ser (c.7C>T) pathogenic?

DPYD p.Pro3Ser (c.7C>T) is classified Uncertain significance in DPYD (ClinVar, Single submitter, 1 submitter; last evaluated 2024-02-26). AlphaMissense: likely benign (0.0768); Ultra-rare (popmax 0.0106%, nfe); Associated with Inborn genetic diseases.

What condition is associated with DPYD p.Pro3Ser (c.7C>T)?

DPYD p.Pro3Ser (c.7C>T) is associated with Inborn genetic diseases (ClinVar).

How common is DPYD p.Pro3Ser (c.7C>T) in the general population?

DPYD p.Pro3Ser (c.7C>T) is ultra-rare (popmax 0.0106%, nfe) (gnomAD).

What do computational predictors say about DPYD p.Pro3Ser (c.7C>T)?

AlphaMissense predicts likely benign (score 0.0768) — an in-silico prediction, not a clinical call.

DPYD p.Pro3Ser

c.7C>T · rs762198241 · VCV2397787

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0768 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0106%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.0768	likely benign
REVEL	0.174	moderately benign-leaning
SaProt	LLR -3.14	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 3.6	GERP 1.7, phastCons 1
Regional constraint	o/e 1.04	unconstrained · MANE · 842 kb · p 0.18 · regional, not allelic
Overall
CADD	17.47	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0106% European (non-Finnish) · 124/1,169,276 alleles

Filtering AF 0.00909% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0085%

Overall 0.0083% 132/1,591,080 alleles · ultra-rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.0106%	9,430
Remaining individualsnot grpmax-eligible	0.00974%	10,262
African / African-American	0.0027%	37,021

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.Pro3Ser
Coding: c.7C>T
MANE Select: NM_000110
dbSNP: rs762198241
Type: single nucleotide variant
Location: chr1:97920916 (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

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

DPYD p.Ala513Val Uncertain significance ★★ ⚠ same condition
DPYD p.Ala664Ser Uncertain significance ★★ ⚠ same condition
DPYD p.Arg332Gln Uncertain significance ★★ ⚠ same condition
DPYD p.Arg410Gln Uncertain significance ★★ ⚠ same condition
DPYD p.Arg692Gln Uncertain significance ★★ ⚠ same condition
DPYD p.Gln508= Uncertain significance ★★ same condition
DPYD p.Glu13Lys Uncertain significance ★★ ⚠ same condition
DPYD p.Glu950Lys Uncertain significance ★★ ⚠ 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-pro3ser (accessed [today's date]).

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