Is DPYD p.Ser175= (c.525G>A) pathogenic?

DPYD p.Ser175= (c.525G>A) is classified Likely benign in DPYD (ClinVar, Multiple submitters, 4 submitters; last evaluated 2024-11-13). Rare (popmax 0.229%, afr); Associated with Inborn genetic diseases.

What condition is associated with DPYD p.Ser175= (c.525G>A)?

DPYD p.Ser175= (c.525G>A) is associated with Inborn genetic diseases (ClinVar).

How common is DPYD p.Ser175= (c.525G>A) in the general population?

DPYD p.Ser175= (c.525G>A) is rare (popmax 0.229%, afr) (gnomAD).

DPYD p.Ser175=

c.525G>A · rs6670886 · VCV100115

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

gnomAD v4.1

Rare

rare (popmax 0.229%, afr)

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 0.32	GERP -2.7, phastCons 0.58
Overall
CADD	6.168	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.229% African / African-American · 172/74,962 alleles

Filtering AF 0.201% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.191%

Overall 0.0128% 207/1,613,364 alleles · rare exomes 108/1,461,272 · genomes 99/152,092 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.229%	436
Middle Eastern	0.0825%	1,212
Remaining individualsnot grpmax-eligible	0.0224%	4,463
East Asian	0.0134%	7,478
Admixed American	0.0133%	7,493
European (non-Finnish)	0.00017%	589,769

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.Ser175=
Coding: c.525G>A
MANE Select: NM_000110
dbSNP: rs6670886
Type: single nucleotide variant
Location: chr1:97699506 (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

Similar variants

DPYD p.Ala513Val Uncertain significance ★★ ⚠ same condition
DPYD p.Ala664Ser Uncertain significance ★★ ⚠ same condition
DPYD p.Arg332Gln Uncertain significance ★★ ⚠ same condition
DPYD p.Arg410Gln Uncertain significance ★★ ⚠ same condition
DPYD p.Arg692Gln Uncertain significance ★★ ⚠ same condition
DPYD p.Gln508= Uncertain significance ★★ same condition
DPYD p.Glu13Lys Uncertain significance ★★ same condition
DPYD p.Glu950Lys 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/dpyd-p-ser175 (accessed [today's date]).

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