Is DPYS p.Arg479Gln (c.1436G>A) pathogenic?

DPYS p.Arg479Gln (c.1436G>A) is classified Uncertain significance in DPYS (ClinVar, Single submitter, 1 submitter; last evaluated 2025-08-20). AlphaMissense: likely benign (0.15); Ultra-rare (popmax 0.033%, mid); Associated with Inborn genetic diseases.

What condition is associated with DPYS p.Arg479Gln (c.1436G>A)?

DPYS p.Arg479Gln (c.1436G>A) is associated with Inborn genetic diseases (ClinVar).

How common is DPYS p.Arg479Gln (c.1436G>A) in the general population?

DPYS p.Arg479Gln (c.1436G>A) is ultra-rare (popmax 0.033%, mid) (gnomAD).

What do computational predictors say about DPYS p.Arg479Gln (c.1436G>A)?

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

DPYS p.Arg479Gln

c.1436G>A · rs369549953 · VCV2599305

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.15 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.033%, mid)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.15	likely benign
REVEL	0.442	indeterminate
SaProt	LLR -12.57	damaging
⇒ SaProt calls this damaging; AlphaMissense does not; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 1.4	GERP 1.1, phastCons 0.99
Regional constraint	o/e 0.97	unconstrained · MANE · 86 kb · p 0.4 · regional, not allelic
Overall
CADD	23.4	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 0.033% Middle Eastern · 2/6,058 alleles

Filtering AF 0.00773% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00624%

Overall 0.00669% 108/1,614,078 alleles · ultra-rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.033%	3,029
Admixed American	0.015%	6,668
European (non-Finnish)	0.00805%	12,421
East Asian	0.00223%	44,892
Remaining individualsnot grpmax-eligible	0.0016%	62,502

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.Arg479Gln
Coding: c.1436G>A
MANE Select: NM_001385
dbSNP: rs369549953
Type: single nucleotide variant
Location: chr8:104392791 (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 479: 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

Similar variants

DPYS p.Ser379Arg Pathogenic/Likely pathogenic ★★ same condition
DPYS p.Ala47Gly Uncertain significance ★★ ⚠ same condition
DPYS p.Ala491Val Uncertain significance ★★ ⚠ same condition
DPYS p.Asn347Ser Uncertain significance ★★ ⚠ same condition
DPYS p.Asp140Asn Uncertain significance ★★ ⚠ same condition
DPYS p.Asp309Tyr Uncertain significance ★★ ⚠ same condition
DPYS p.Glu115Lys Uncertain significance ★★ ⚠ same condition
DPYS p.Gly216Asp Uncertain significance ★★ ⚠ 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-arg479gln (accessed [today's date]).

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