Is DRD4 p.Ala311= (c.933T>G) pathogenic?

DRD4 p.Ala311= (c.933T>G) is classified Conflicting classifications of pathogenicity in DRD4 (ClinVar, Conflicting submitters, 2 submitters; last evaluated 2025-04-01). Ultra-rare (popmax 0.0691%, afr); Associated with hereditary attention deficit-hyperactivity disorder.

What condition is associated with DRD4 p.Ala311= (c.933T>G)?

DRD4 p.Ala311= (c.933T>G) is associated with hereditary attention deficit-hyperactivity disorder (ClinVar).

How common is DRD4 p.Ala311= (c.933T>G) in the general population?

DRD4 p.Ala311= (c.933T>G) is ultra-rare (popmax 0.0691%, afr) (gnomAD).

DRD4 p.Ala311=

c.933T>G · rs547842677 · VCV2507405

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0691%, afr)

Conditions

hereditary attention deficit-hyperactivity disorder

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 -7.6	GERP -1.9
Overall
CADD	2.047	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0691% African / African-American · 44/63,658 alleles

Filtering AF 0.0542% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.049%

Overall 0.014% 210/1,503,462 alleles · ultra-rare exomes 154/1,372,706 · genomes 56/130,756 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0691%	1,447
South Asian	0.0684%	1,461
Middle Eastern	0.0467%	2,142
East Asian	0.0346%	2,889
Admixed American	0.0167%	5,986
Remaining individualsnot grpmax-eligible	0.0153%	6,552
European (non-Finnish)	0.00653%	15,316
Finnishnot grpmax-eligible	0.00469%	21,336

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.Ala311=
Coding: c.933T>G
MANE Select: NM_000797
dbSNP: rs547842677
Type: single nucleotide variant
Location: chr11:640182 (GRCh38)
Gene constraint: LOEUF 1.952 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 78.06 · 2 PDB
Residue 311: 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

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.Arg271Gln Uncertain significance ★ ⚠ same condition
DRD4 p.Gln287Pro Conflicting classifications of pathogenicity ★ ⚠ same condition
DRD4 p.Gly272= 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-ala311 (accessed [today's date]).

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