Is DRD4 p.Ser284Arg (c.850A>C) pathogenic?

DRD4 p.Ser284Arg (c.850A>C) is classified Likely benign in DRD4 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-12-01). AlphaMissense: likely benign (0.138); Rare (popmax 0.315%, sas).

How common is DRD4 p.Ser284Arg (c.850A>C) in the general population?

DRD4 p.Ser284Arg (c.850A>C) is rare (popmax 0.315%, sas) (gnomAD).

What do computational predictors say about DRD4 p.Ser284Arg (c.850A>C)?

AlphaMissense predicts likely benign (score 0.138) — an in-silico prediction, not a clinical call.

DRD4 p.Ser284Arg

c.850A>C · VCV4681296

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.138 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.315%, sas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.138	likely benign
REVEL	0.043	moderately benign-leaning
SaProt	LLR -3.17	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP -1.1	GERP -2.2
Regional constraint	o/e 1.44	unconstrained · MANE · 3,295 bp · p 6.5e-29 · regional, not allelic
Overall
CADD	0.742	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 0.315% South Asian · 122/38,754 alleles

Filtering AF 0.269% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.252%

Overall 0.078% 753/965,700 alleles · rare exomes 698/869,616 · genomes 55/96,084 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.315%	318
Remaining individualsnot grpmax-eligible	0.151%	661
East Asian	0.121%	829
Finnishnot grpmax-eligible	0.1%	1,000
Middle Eastern	0.0765%	1,308
European (non-Finnish)	0.0674%	1,484
Admixed American	0.0343%	2,913
African / African-American	0.0123%	8,116
Ashkenazi Jewishnot grpmax-eligible	0.00693%	14,438

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.Ser284Arg
Coding: c.850A>C
MANE Select: NM_000797
Type: single nucleotide variant
Location: chr11:640099 (GRCh38)
Gene constraint: LOEUF 1.952 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 78.06 · 2 PDB
Residue 284: 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); a UniProt-annotated variant site (in allele d4.7)

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

Similar variants

DRD4 p.Ser284Gly Uncertain significance ★ ⚠ same residue
DRD4 p.Ser284_Pro299del Benign same residue
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

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-ser284arg (accessed [today's date]).

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