Is DPYS p.Leu7Val (c.19C>G) pathogenic?

DPYS p.Leu7Val (c.19C>G) is classified Likely benign in DPYS (ClinVar, Multiple submitters, 5 submitters; last evaluated 2026-01-27). AlphaMissense: likely benign (0.1084); Low-frequency (popmax 4.3%, afr); Associated with dihydropyrimidinuria.

What condition is associated with DPYS p.Leu7Val (c.19C>G)?

DPYS p.Leu7Val (c.19C>G) is associated with dihydropyrimidinuria (ClinVar).

How common is DPYS p.Leu7Val (c.19C>G) in the general population?

DPYS p.Leu7Val (c.19C>G) is low-frequency (popmax 4.3%, afr) (gnomAD).

How is Dihydropyrimidinuria inherited?

Typically Autosomal recessive (Orphanet). A genetic counselor can assess individual risk for a family.

What do computational predictors say about DPYS p.Leu7Val (c.19C>G)?

AlphaMissense predicts likely benign (score 0.1084) — an in-silico prediction, not a clinical call.

DPYS p.Leu7Val

c.19C>G · rs57732538 · VCV100149

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 5 submitters

AlphaMissense

likely benign

0.1084 · ACMG-weighted

gnomAD v4.1

Rare

low-frequency (popmax 4.3%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

dihydropyrimidinuria

Computational evidence

Protein change
AlphaMissense	0.1084	likely benign
REVEL	0.289	benign-leaning
SaProt	LLR -8.70	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 5.2	GERP -3.1, phastCons 1
Regional constraint	o/e 0.97	unconstrained · MANE · 86 kb · p 0.4 · regional, not allelic
Overall
CADD	16.77	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 4.3% African / African-American · 2,982/69,280 alleles

Filtering AF 4.18% ClinGen BA1/BS1 input FAF95, joint · FAF99 4.12%

Overall 0.225% 3,377/1,502,416 alleles · low-frequency

Ancestry group	Frequency	1 in
African / African-Americangrpmax	4.3%	23
Remaining individualsnot grpmax-eligible	0.329%	304
Middle Eastern	0.269%	371
Admixed American	0.224%	447
South Asian	0.0174%	5,738
European (non-Finnish)	0.0061%	16,404

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: DPYS
Protein: p.Leu7Val
Coding: c.19C>G
MANE Select: NM_001385
dbSNP: rs57732538
Type: single nucleotide variant
Location: chr8:104466902 (GRCh38)
Gene constraint: LOEUF 1.029 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 96.00 · 1 PDB
Residue 7: a β-strand

Full DPYS gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

dihydropyrimidinuria — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Dihydropyrimidinuria (Orphanet):

Inheritance: Autosomal recessive
Onset: Childhood, Infancy
Prevalence: <1 / 1 000 000 (Worldwide)

Similar variants

DPYS p.Leu7= Likely benign ★★ same residue
DPYS p.Arg302Gln Likely pathogenic ★★ same condition
DPYS p.Arg302Ter Pathogenic/Likely pathogenic ★★ same condition
DPYS p.Arg465Ter Pathogenic ★★ same condition
DPYS p.Arg475Ter Pathogenic/Likely pathogenic ★★ same condition
DPYS p.Arg490Cys Pathogenic/Likely pathogenic ★★ same condition
DPYS p.Arg490His Pathogenic/Likely pathogenic ★★ same condition
DPYS p.Gln190Ter 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/dpys-p-leu7val (accessed [today's date]).

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