Is DPYD p.Val507Ala (c.1520T>C) pathogenic?

DPYD p.Val507Ala (c.1520T>C) is classified Uncertain significance in DPYD (ClinVar, Single submitter, 1 submitter; last evaluated 2024-05-01). AlphaMissense: ambiguous (0.4001); Absent from gnomAD v4.1.

How common is DPYD p.Val507Ala (c.1520T>C) in the general population?

DPYD p.Val507Ala (c.1520T>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about DPYD p.Val507Ala (c.1520T>C)?

AlphaMissense predicts ambiguous (score 0.4001) — an in-silico prediction, not a clinical call.

DPYD p.Val507Ala

c.1520T>C · rs2524372985 · VCV3239416

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.4001 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Computational evidence

Protein change
AlphaMissense	0.4001	ambiguous
REVEL	0.426	indeterminate
SaProt	LLR -12.08	damaging
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 11	GERP 1.9, phastCons 1
Regional constraint	o/e 1.04	unconstrained · MANE · 842 kb · p 0.18 · regional, not allelic
Overall
CADD	23.1	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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: DPYD
Protein: p.Val507Ala
Coding: c.1520T>C
MANE Select: NM_000110
dbSNP: rs2524372985
Type: single nucleotide variant
Location: chr1:97549564 (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

Similar variants

DPYD p.Val507Ile Likely benign ★ same residue
DPYD c.1340-2A>C Likely pathogenic ★★ same type
DPYD c.1905+1G>C Pathogenic/Likely pathogenic ★★ same type
DPYD c.233+1G>T Likely pathogenic ★★ same type
DPYD c.2622+1G>A Likely pathogenic ★★ same type
DPYD c.2767-1G>A Likely pathogenic ★★ same type
DPYD c.680+1G>T Likely pathogenic ★★ same type
DPYD p.Arg21Ter Pathogenic/Likely pathogenic ★★ same type

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-val507ala (accessed [today's date]).

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