Is DPYS p.Ser379Arg (c.1137C>A) pathogenic?

DPYS p.Ser379Arg (c.1137C>A) is classified Pathogenic/Likely pathogenic in DPYS (ClinVar, Multiple submitters, 10 submitters; last evaluated 2025-09-12). AlphaMissense: likely pathogenic (0.9989); Ultra-rare (popmax 0.0987%, mid); Associated with Inborn genetic diseases.

What condition is associated with DPYS p.Ser379Arg (c.1137C>A)?

DPYS p.Ser379Arg (c.1137C>A) is associated with Inborn genetic diseases, dihydropyrimidinuria (ClinVar).

How common is DPYS p.Ser379Arg (c.1137C>A) in the general population?

DPYS p.Ser379Arg (c.1137C>A) is ultra-rare (popmax 0.0987%, mid) (gnomAD).

What do computational predictors say about DPYS p.Ser379Arg (c.1137C>A)?

AlphaMissense predicts likely pathogenic (score 0.9989) — an in-silico prediction, not a clinical call.

DPYS p.Ser379Arg

c.1137C>A · rs201258823 · VCV372797

Pathogenic/Likely pathogenic Multiple submitters

Classification

Pathogenic/Likely pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 10 submitters

AlphaMissense

likely pathogenic

0.9989 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0987%, mid)

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.9989	likely pathogenic ✓ concordant with ClinVar · top 1% in DPYS
REVEL	0.915	moderately pathogenic-leaning
SaProt	LLR -15.44	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 4.7	GERP 1.1, phastCons 1
Regional constraint	o/e 0.97	unconstrained · MANE · 86 kb · p 0.4 · regional, not allelic
Overall
CADD	25.0	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 0.0987% Middle Eastern · 6/6,082 alleles

Filtering AF 0.0429% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0293%

Overall 0.0139% 225/1,613,874 alleles · ultra-rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0987%	1,014
Remaining individualsnot grpmax-eligible	0.0208%	4,806
European (non-Finnish)	0.0168%	5,960
African / African-American	0.00801%	12,487
Ashkenazi Jewishnot grpmax-eligible	0.00338%	29,604
Admixed American	0.00167%	60,000

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.Ser379Arg
Coding: c.1137C>A
MANE Select: NM_001385
dbSNP: rs201258823
Type: single nucleotide variant
Location: chr8:104424345 (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 379: an α-helix

Full DPYS 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: dihydropyrimidinuria

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-ser379arg (accessed [today's date]).

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