Is DRD4 p.Val352= (c.1056C>G) pathogenic?

DRD4 p.Val352= (c.1056C>G) is classified Benign in DRD4 (ClinVar, No assertion criteria, 2 submitters; last evaluated 2019-03-21). Common (popmax 5.41%, afr) — too common for a highly-penetrant pathogenic allele; Associated with DRD4-related disorder.

What condition is associated with DRD4 p.Val352= (c.1056C>G)?

DRD4 p.Val352= (c.1056C>G) is associated with DRD4-related disorder (ClinVar).

DRD4 p.Val352=

Q: How common is DRD4 p.Val352= (c.1056C>G) in the general population?

DRD4 p.Val352= (c.1056C>G) is common (popmax 5.41%, afr) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.1056C>G · rs201878429 · VCV3056794

Benign No assertion criteria

Classification

Benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 2 submitters

gnomAD v4.1

Common

common (popmax 5.41%, afr) — too common for a highly-penetrant pathogenic allele

Conditions

DRD4-related disorder

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation/SpliceAI carries the signal.
Splicing
SpliceAI	Δ0.36	donor gain · deltas
Pangolin	Δ0.26	gain · loss 0.25 · agrees with SpliceAI · independent
Constraint at this position
Conservation	phyloP -0.027	GERP -2.1, phastCons 0.81
Overall
CADD	15.74	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 5.41% African / African-American · 3,965/73,256 alleles

Filtering AF 5.27% ClinGen BA1/BS1 input FAF95, joint · FAF99 5.21%

Overall 0.312% 4,690/1,504,480 alleles · common exomes 2,267/1,354,314 · genomes 2,423/150,166 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	5.41%	18
Admixed American	0.445%	225
Remaining individualsnot grpmax-eligible	0.43%	232
Middle Eastern	0.115%	867
European (non-Finnish)	0.0204%	4,904
South Asian	0.0144%	6,960

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.Val352=
Coding: c.1056C>G
MANE Select: NM_000797
dbSNP: rs201878429
Type: single nucleotide variant
Location: chr11:640305 (GRCh38)
Gene constraint: LOEUF 1.952 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 78.06 · 2 PDB
Residue 352: an α-helix

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

Disease context

DRD4-related disorder

Similar variants

DRD4 p.Ala36Val Uncertain significance ★ ⚠ same condition
DRD4 p.Cys372Tyr Uncertain significance ⚠ same condition
DRD4 p.Pro246His Uncertain significance ⚠ same condition
DRD4 c.285+7C>T Likely benign same condition
DRD4 p.Ala228= Likely benign same condition
DRD4 p.Ala78Thr Likely benign same condition
DRD4 p.Ala84Thr Benign ⚠ same condition
DRD4 p.Arg412Leu Likely benign 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-val352 (accessed [today's date]).

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