Is DPYD p.Ala513Val (c.1538C>T) pathogenic?

DPYD p.Ala513Val (c.1538C>T) is classified Uncertain significance in DPYD (ClinVar, Multiple submitters, 3 submitters; last evaluated 2023-04-11). AlphaMissense: likely benign (0.0705); Ultra-rare (popmax 0.0329%, mid); Associated with Inborn genetic diseases.

What condition is associated with DPYD p.Ala513Val (c.1538C>T)?

DPYD p.Ala513Val (c.1538C>T) is associated with Inborn genetic diseases, dihydropyrimidine dehydrogenase deficiency (ClinVar).

How common is DPYD p.Ala513Val (c.1538C>T) in the general population?

DPYD p.Ala513Val (c.1538C>T) is ultra-rare (popmax 0.0329%, mid) (gnomAD).

What do computational predictors say about DPYD p.Ala513Val (c.1538C>T)?

AlphaMissense predicts likely benign (score 0.0705) — an in-silico prediction, not a clinical call.

DPYD p.Ala513Val

c.1538C>T · rs760663364 · VCV558310

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

AlphaMissense

likely benign

0.0705 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0329%, mid)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.0705	likely benign
REVEL	0.159	moderately benign-leaning
SaProt	LLR -5.39	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 3.4	GERP 0.68, phastCons 0.98
Regional constraint	o/e 1.04	unconstrained · MANE · 842 kb · p 0.18 · regional, not allelic
Overall
CADD	13.1	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 0.0329% Middle Eastern · 2/6,080 alleles

Filtering AF 0.0058% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00241%

Overall 0.000372% 6/1,612,254 alleles · ultra-rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0329%	3,040
African / African-American	0.00267%	37,396
Remaining individualsnot grpmax-eligible	0.0016%	62,374
European (non-Finnish)	8.48e-05%	1,178,976

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.Ala513Val
Coding: c.1538C>T
MANE Select: NM_000110
dbSNP: rs760663364
Type: single nucleotide variant
Location: chr1:97515928 (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

Also linked: dihydropyrimidine dehydrogenase deficiency

Similar variants

DPYD p.Ala513Gly Uncertain significance ★ ⚠ same residue
DPYD p.Ala513Pro 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

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-ala513val (accessed [today's date]).

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