Is DRD4 p.Gln287Pro (c.860A>C) pathogenic?

DRD4 p.Gln287Pro (c.860A>C) is classified Conflicting classifications of pathogenicity in DRD4 (ClinVar, Conflicting submitters, 5 submitters). AlphaMissense: likely benign (0.0432); Common (popmax 13.3%, afr) — too common for a highly-penetrant pathogenic allele; Associated with hereditary attention deficit-hyperactivity disorder.

What condition is associated with DRD4 p.Gln287Pro (c.860A>C)?

DRD4 p.Gln287Pro (c.860A>C) is associated with hereditary attention deficit-hyperactivity disorder (ClinVar).

What do computational predictors say about DRD4 p.Gln287Pro (c.860A>C)?

AlphaMissense predicts likely benign (score 0.0432) — an in-silico prediction, not a clinical call.

DRD4 p.Gln287Pro

Q: How common is DRD4 p.Gln287Pro (c.860A>C) in the general population?

DRD4 p.Gln287Pro (c.860A>C) is common (popmax 13.3%, afr) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.860A>C · rs769762387 · VCV1206183

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 5 submitters

AlphaMissense

likely benign

0.0432 · ACMG-weighted

gnomAD v4.1

Common

common (popmax 13.3%, afr) — too common for a highly-penetrant pathogenic allele

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

hereditary attention deficit-hyperactivity disorder

Computational evidence

Protein change
AlphaMissense	0.0432	likely benign
REVEL	0.084	moderately benign-leaning
SaProt	LLR -4.40	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -2	GERP -2.2
Regional constraint	o/e 1.44	unconstrained · MANE · 3,295 bp · p 6.5e-29 · regional, not allelic
Overall
CADD	0.336	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 13.3% African / African-American · 4,748/35,622 alleles

Filtering AF 13% ClinGen BA1/BS1 input FAF95, joint · FAF99 12.9%

Overall 10.7% 118,155/1,108,258 alleles · common exomes 109,865/1,033,632 · genomes 8,290/74,626 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	13.3%	8
European (non-Finnish)	12.1%	8
Remaining individualsnot grpmax-eligible	7.82%	13
Amishnot grpmax-eligible	7.23%	14
Ashkenazi Jewishnot grpmax-eligible	5.69%	18
Admixed American	5.11%	20
Middle Eastern	4.3%	23
Finnishnot grpmax-eligible	2.56%	39
South Asian	1.76%	57
East Asian	0.155%	647

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.Gln287Pro
Coding: c.860A>C
MANE Select: NM_000797
dbSNP: rs769762387
Type: single nucleotide variant
Location: chr11:640109 (GRCh38)
Gene constraint: LOEUF 1.952 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 78.06 · 2 PDB
Residue 287: the '4 x 16 aa approximate tandem repeats of [pa]-a-p-g-l-p-[pqr]-[dg]-p-c-g-p-d-c-a-p' region; a UniProt-annotated variant site (in allele d4.2)

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.Gln287Arg Uncertain significance ★ ⚠ same residue
DRD4 p.Asn309Asp Uncertain significance ★★ ⚠ same condition
DRD4 p.Ser308Pro Uncertain significance ★★ ⚠ 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
DRD4 p.Arg271Gln 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/drd4-p-gln287pro (accessed [today's date]).

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