Is DRD4 p.Leu285= (c.855C>T) pathogenic?

DRD4 p.Leu285= (c.855C>T) is classified Likely benign in DRD4 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-07-01). Ultra-rare (popmax 0.0805%, afr).

How common is DRD4 p.Leu285= (c.855C>T) in the general population?

DRD4 p.Leu285= (c.855C>T) is ultra-rare (popmax 0.0805%, afr) (gnomAD).

DRD4 p.Leu285=

c.855C>T · rs745991309 · VCV2641083

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.0805%, afr)

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 -2.7	GERP -2.2
Overall
CADD	0.44	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0805% African / African-American · 48/59,624 alleles

Filtering AF 0.0623% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0559%

Overall 0.0302% 379/1,254,944 alleles · ultra-rare exomes 279/1,119,212 · genomes 100/135,732 · joint denominator

Ancestry group	Frequency	1 in
Amishnot grpmax-eligible	0.971%	103
African / African-Americangrpmax	0.0805%	1,242
East Asian	0.0696%	1,436
Ashkenazi Jewishnot grpmax-eligible	0.0586%	1,707
Admixed American	0.0577%	1,733
Middle Eastern	0.0571%	1,752
South Asian	0.0306%	3,269
European (non-Finnish)	0.0245%	4,075
Finnishnot grpmax-eligible	0.0212%	4,708
Remaining individualsnot grpmax-eligible	0.0187%	5,339

Amish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Leu285=
Coding: c.855C>T
MANE Select: NM_000797
dbSNP: rs745991309
Type: single nucleotide variant
Location: chr11:640104 (GRCh38)
Gene constraint: LOEUF 1.952 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 78.06 · 2 PDB
Residue 285: 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

Similar variants

DRD4 p.Asn309Asp Uncertain significance ★★ ⚠ same type
DRD4 p.Ser308Pro Uncertain significance ★★ ⚠ same type
DRD4 p.Ala335Gly Benign ★★ same type
DRD4 p.Gly11Arg Benign ★★ same type
DRD4 p.Leu83= Likely benign ★★ same type
DRD4 p.Pro244= Likely benign ★★ same type
DRD4 p.Pro248= Likely benign ★★ same type
DRD4 p.Val398= Likely benign ★★ same type

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-leu285 (accessed [today's date]).

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