Is DPYS p.Arg6Gln (c.17G>A) pathogenic?

DPYS p.Arg6Gln (c.17G>A) is classified Benign/Likely benign in DPYS (ClinVar, Multiple submitters, 3 submitters; last evaluated 2025-10-02). AlphaMissense: likely benign (0.15); Rare (popmax 0.232%, eas); Associated with dihydropyrimidinuria.

What condition is associated with DPYS p.Arg6Gln (c.17G>A)?

DPYS p.Arg6Gln (c.17G>A) is associated with dihydropyrimidinuria (ClinVar).

How common is DPYS p.Arg6Gln (c.17G>A) in the general population?

DPYS p.Arg6Gln (c.17G>A) is rare (popmax 0.232%, eas) (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.Arg6Gln (c.17G>A)?

AlphaMissense predicts likely benign (score 0.15) — an in-silico prediction, not a clinical call.

DPYS p.Arg6Gln

c.17G>A · rs199618701 · VCV361455

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

AlphaMissense

likely benign

0.15 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.232%, eas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

dihydropyrimidinuria

Computational evidence

Protein change
AlphaMissense	0.15	likely benign
REVEL	0.161	moderately benign-leaning
SaProt	LLR -7.94	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 0.3	GERP -0.25
Regional constraint	o/e 0.97	unconstrained · MANE · 86 kb · p 0.4 · regional, not allelic
Overall
CADD	14.49	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 0.232% East Asian · 87/37,508 alleles

Filtering AF 0.193% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.178%

Overall 0.0338% 507/1,499,708 alleles · rare

Ancestry group	Frequency	1 in
Ashkenazi Jewishnot grpmax-eligible	0.304%	329
East Asiangrpmax	0.232%	431
Remaining individualsnot grpmax-eligible	0.0961%	1,040
European (non-Finnish)	0.0235%	4,250
Middle Eastern	0.0209%	4,782
South Asian	0.0112%	8,889
Admixed American	0.00631%	15,847
African / African-American	0.00289%	34,570
Finnishnot grpmax-eligible	0.00227%	44,088

Ashkenazi Jewish 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: DPYS
Protein: p.Arg6Gln
Coding: c.17G>A
MANE Select: NM_001385
dbSNP: rs199618701
Type: single nucleotide variant
Location: chr8:104466904 (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 6: 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.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
DPYS p.Gln334Arg 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-arg6gln (accessed [today's date]).

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