Is DPYD p.Pro1018Ala (c.3052C>G) pathogenic?

DPYD p.Pro1018Ala (c.3052C>G) is classified Uncertain significance in DPYD (ClinVar, Single submitter, 1 submitter; last evaluated 2021-11-29). AlphaMissense: likely benign (0.0757); Very rare (popmax 0.00186%, nfe); Associated with Inborn genetic diseases.

What condition is associated with DPYD p.Pro1018Ala (c.3052C>G)?

DPYD p.Pro1018Ala (c.3052C>G) is associated with Inborn genetic diseases (ClinVar).

How common is DPYD p.Pro1018Ala (c.3052C>G) in the general population?

DPYD p.Pro1018Ala (c.3052C>G) is very rare (popmax 0.00186%, nfe) (gnomAD).

What do computational predictors say about DPYD p.Pro1018Ala (c.3052C>G)?

AlphaMissense predicts likely benign (score 0.0757) — an in-silico prediction, not a clinical call.

DPYD p.Pro1018Ala

c.3052C>G · rs956842768 · VCV1799278

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0757 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00186%, nfe)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.0757	likely benign
REVEL	0.618	indeterminate
SaProt	LLR -6.75	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 2.6, phastCons 1
Regional constraint	o/e 1.04	unconstrained · MANE · 842 kb · p 0.18 · regional, not allelic
Overall
CADD	22.5	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 0.00186% European (non-Finnish) · 22/1,179,686 alleles

Filtering AF 0.00122% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00104%

Overall 0.00149% 24/1,613,552 alleles · very rare

Ancestry group	Frequency	1 in
Remaining individualsnot grpmax-eligible	0.0032%	31,227
European (non-Finnish)grpmax	0.00186%	53,622

Remaining individuals shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Pro1018Ala
Coding: c.3052C>G
MANE Select: NM_000110
dbSNP: rs956842768
Type: single nucleotide variant
Location: chr1:97079002 (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-pro1018ala (accessed [today's date]).

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