Is DRD4 p.Arg271Gln (c.812G>A) pathogenic?

DRD4 p.Arg271Gln (c.812G>A) is classified Uncertain significance in DRD4 (ClinVar, Single submitter, 2 submitters). AlphaMissense: likely benign (0.0645); Low-frequency (popmax 4.51%, eas); Associated with hereditary attention deficit-hyperactivity disorder.

What condition is associated with DRD4 p.Arg271Gln (c.812G>A)?

DRD4 p.Arg271Gln (c.812G>A) is associated with hereditary attention deficit-hyperactivity disorder (ClinVar).

How common is DRD4 p.Arg271Gln (c.812G>A) in the general population?

DRD4 p.Arg271Gln (c.812G>A) is low-frequency (popmax 4.51%, eas) (gnomAD).

What do computational predictors say about DRD4 p.Arg271Gln (c.812G>A)?

AlphaMissense predicts likely benign (score 0.0645) — an in-silico prediction, not a clinical call.

DRD4 p.Arg271Gln

c.812G>A · rs767239460 · VCV2507413

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.0645 · ACMG-weighted

gnomAD v4.1

Rare

low-frequency (popmax 4.51%, eas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

hereditary attention deficit-hyperactivity disorder

Computational evidence

Protein change
AlphaMissense	0.0645	likely benign
REVEL	0.042	moderately benign-leaning
SaProt	LLR -3.48	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 -1	GERP -2.2
Regional constraint	o/e 1.44	unconstrained · MANE · 3,295 bp · p 6.5e-29 · regional, not allelic
Overall
CADD	1.799	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 4.51% East Asian · 498/11,048 alleles

Filtering AF 4.18% ClinGen BA1/BS1 input FAF95, joint · FAF99 4.05%

Overall 0.347% 3,083/889,620 alleles · low-frequency exomes 2,991/834,150 · genomes 92/55,470 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	4.51%	22
European (non-Finnish)	0.318%	314
Finnishnot grpmax-eligible	0.26%	384
Remaining individualsnot grpmax-eligible	0.23%	436
Ashkenazi Jewishnot grpmax-eligible	0.173%	579
Admixed American	0.142%	704
South Asian	0.0876%	1,141
African / African-American	0.0521%	1,921
Middle Eastern	0.0489%	2,046

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.Arg271Gln
Coding: c.812G>A
MANE Select: NM_000797
dbSNP: rs767239460
Type: single nucleotide variant
Location: chr11:640061 (GRCh38)
Gene constraint: LOEUF 1.952 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 78.06 · 2 PDB
Residue 271: 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.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.Arg271fs Uncertain significance ★ same residue
DRD4 p.Gln287Pro 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-arg271gln (accessed [today's date]).

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