Is DPYD p.Ile704Phe (c.2110A>T) pathogenic?

DPYD p.Ile704Phe (c.2110A>T) is classified Uncertain significance in DPYD (ClinVar, Single submitter, 1 submitter; last evaluated 2024-08-06). AlphaMissense: likely benign (0.3255); Very rare (popmax 6.85e-05%); Associated with Inborn genetic diseases.

What condition is associated with DPYD p.Ile704Phe (c.2110A>T)?

DPYD p.Ile704Phe (c.2110A>T) is associated with Inborn genetic diseases (ClinVar).

How common is DPYD p.Ile704Phe (c.2110A>T) in the general population?

DPYD p.Ile704Phe (c.2110A>T) is very rare (popmax 6.85e-05%) (gnomAD).

What do computational predictors say about DPYD p.Ile704Phe (c.2110A>T)?

AlphaMissense predicts likely benign (score 0.3255) — an in-silico prediction, not a clinical call.

DPYD p.Ile704Phe

c.2110A>T · VCV3505089

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.3255 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 6.85e-05%)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.3255	likely benign
REVEL	0.481	indeterminate
SaProt	LLR -14.04	damaging
⇒ SaProt calls this damaging; AlphaMissense does not; REVEL makes no call.
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP -1.7	GERP -3.7
Regional constraint	o/e 1.04	unconstrained · MANE · 842 kb · p 0.18 · regional, not allelic
Overall
CADD	18.99	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 6.85e-05%

Overall 6.85e-05% 1/1,460,454 alleles · very rare

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.Ile704Phe
Coding: c.2110A>T
Type: single nucleotide variant
Location: chr1:97306246 (GRCh38)

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

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-ile704phe (accessed [today's date]).

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