Is DPYD p.Lys7= (c.21G>A) pathogenic?

DPYD p.Lys7= (c.21G>A) is classified Likely benign in DPYD (ClinVar, Single submitter, 1 submitter; last evaluated 2023-11-30). Very rare (popmax 0.0094%, nfe); Associated with Inborn genetic diseases.

What condition is associated with DPYD p.Lys7= (c.21G>A)?

DPYD p.Lys7= (c.21G>A) is associated with Inborn genetic diseases (ClinVar).

How common is DPYD p.Lys7= (c.21G>A) in the general population?

DPYD p.Lys7= (c.21G>A) is very rare (popmax 0.0094%, nfe) (gnomAD).

DPYD p.Lys7=

c.21G>A · rs774730464 · VCV3230326

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.0094%, 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 2.9	GERP 1.7, phastCons 1
Overall
CADD	13.9	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0094% European (non-Finnish) · 110/1,170,600 alleles

Filtering AF 0.00797% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00741%

Overall 0.00734% 117/1,593,690 alleles · very rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.0094%	10,642
Remaining individualsnot grpmax-eligible	0.00811%	12,333
Admixed American	0.00172%	58,184
African / African-American	0.00135%	74,094

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.Lys7=
Coding: c.21G>A
MANE Select: NM_000110
dbSNP: rs774730464
Type: single nucleotide variant
Location: chr1:97920902 (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-lys7 (accessed [today's date]).

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