Is DPYD p.Ala683= (c.2049C>G) pathogenic?

DPYD p.Ala683= (c.2049C>G) is classified Conflicting classifications of pathogenicity in DPYD (ClinVar, Conflicting submitters, 5 submitters; last evaluated 2024-09-10). Rare (popmax 0.232%, eas); Associated with Inborn genetic diseases.

What condition is associated with DPYD p.Ala683= (c.2049C>G)?

DPYD p.Ala683= (c.2049C>G) is associated with Inborn genetic diseases, dihydropyrimidine dehydrogenase deficiency (ClinVar).

How common is DPYD p.Ala683= (c.2049C>G) in the general population?

DPYD p.Ala683= (c.2049C>G) is rare (popmax 0.232%, eas) (gnomAD).

DPYD p.Ala683=

c.2049C>G · rs183475941 · VCV100084

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 5 submitters

gnomAD v4.1

Rare

rare (popmax 0.232%, eas)

Conditions

Inborn genetic diseases

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 1.3	GERP -1.6, phastCons 1
Overall
CADD	3.106	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.232% East Asian · 104/44,846 alleles

Filtering AF 0.196% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.182%

Overall 0.00899% 145/1,613,592 alleles · rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.232%	431
Remaining individualsnot grpmax-eligible	0.056%	1,785
Admixed American	0.00333%	30,001
South Asian	0.0022%	45,438
African / African-American	0.00133%	75,032
European (non-Finnish)	8.48e-05%	1,179,791

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.Ala683=
Coding: c.2049C>G
MANE Select: NM_000110
dbSNP: rs183475941
Type: single nucleotide variant
Location: chr1:97373570 (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.Ala683Thr 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
DPYD p.Arg21Ter Pathogenic/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-ala683 (accessed [today's date]).

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