Is DPYD p.Cys87= (c.261T>C) pathogenic?

DPYD p.Cys87= (c.261T>C) is classified Likely benign in DPYD (ClinVar, Single submitter, 1 submitter; last evaluated 2023-02-26). Very rare (popmax 0.00288%, nfe); Associated with Inborn genetic diseases.

What condition is associated with DPYD p.Cys87= (c.261T>C)?

DPYD p.Cys87= (c.261T>C) is associated with Inborn genetic diseases (ClinVar).

How common is DPYD p.Cys87= (c.261T>C) in the general population?

DPYD p.Cys87= (c.261T>C) is very rare (popmax 0.00288%, nfe) (gnomAD).

DPYD p.Cys87=

c.261T>C · rs1056815262 · VCV2494416

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00288%, nfe)

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 3	GERP -1.1, phastCons 1
Overall
CADD	8.642	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00288% European (non-Finnish) · 34/1,179,502 alleles

Filtering AF 0.00208% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00183%

Overall 0.00217% 35/1,613,076 alleles · very rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00288%	34,691
Remaining individualsnot grpmax-eligible	0.0016%	62,456

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.Cys87=
Coding: c.261T>C
MANE Select: NM_000110
dbSNP: rs1056815262
Type: single nucleotide variant
Location: chr1:97740452 (GRCh38)
Gene constraint: LOEUF 1.09 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 96.23
Residue 87: the 4fe-4s ferredoxin-type 1 domain; a binding site

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-cys87 (accessed [today's date]).

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