Is DRD4 p.Pro18fs (c.52_62del) pathogenic?

DRD4 p.Pro18fs (c.5262del) is classified Uncertain significance in DRD4 (ClinVar, Single submitter, 1 submitter). Ultra-rare (popmax 0.0173%, sas); Associated with hereditary attention deficit-hyperactivity disorder.

What condition is associated with DRD4 p.Pro18fs (c.52_62del)?

DRD4 p.Pro18fs (c.52_62del) is associated with hereditary attention deficit-hyperactivity disorder (ClinVar).

How common is DRD4 p.Pro18fs (c.52_62del) in the general population?

DRD4 p.Pro18fs (c.52_62del) is ultra-rare (popmax 0.0173%, sas) (gnomAD).

DRD4 p.Pro18fs

c.52_62del · rs1279080134 · VCV2585270

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

ultra-rare (popmax 0.0173%, sas)

Conditions

hereditary attention deficit-hyperactivity disorder

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function
NMD	predicted	premature termination codon in exon 1 of 4
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 0.27	GERP -2.7, phastCons 0.002
Region caveats
Repeat context	tandem	G-rich low complexity · ambiguous alignment · confidence, not pathogenicity

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0173% South Asian · 7/40,414 alleles

Filtering AF 0.00807% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0057%

Overall 0.00062% 8/1,290,956 alleles · ultra-rare exomes 8/1,140,180 · genomes 0/150,776 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0173%	5,773
Remaining individualsnot grpmax-eligible	0.00207%	48,286

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: DRD4
Protein: p.Pro18fs
Coding: c.52_62del
MANE Select: NM_000797
dbSNP: rs1279080134
Type: Deletion
Location: chr11:637350 (GRCh38)
Gene constraint: LOEUF 1.952 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 78.06 · 2 PDB

Full DRD4 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

hereditary attention deficit-hyperactivity disorder — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

DRD4 p.Gln255fs Uncertain significance ★★ same condition
DRD4 p.Asn309Asp Uncertain significance ★★ ⚠ same condition
DRD4 p.Ser308Pro Uncertain significance ★★ ⚠ same condition
DRD4 p.Asn52fs Likely pathogenic ★ same condition
DRD4 c.1058-32G>C Uncertain significance ★ same condition
DRD4 c.285+2T>G Uncertain significance ★ same condition
DRD4 c.-11C>T Uncertain significance ★ same condition
DRD4 p.Ala311= Conflicting classifications of pathogenicity ★ 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/drd4-p-pro18fs (accessed [today's date]).

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