Is DRD4 p.Ser239Thr (c.716G>C) pathogenic?

DRD4 p.Ser239Thr (c.716G>C) is classified Uncertain significance in DRD4 (ClinVar, Single submitter, 1 submitter; last evaluated 2021-10-12). AlphaMissense: likely benign (0.1169); Absent from gnomAD v4.1.

How common is DRD4 p.Ser239Thr (c.716G>C) in the general population?

DRD4 p.Ser239Thr (c.716G>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about DRD4 p.Ser239Thr (c.716G>C)?

AlphaMissense predicts likely benign (score 0.1169) — an in-silico prediction, not a clinical call.

DRD4 p.Ser239Thr

c.716G>C · rs2133251867 · VCV2389554

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1169 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1169	likely benign
REVEL	0.113	moderately benign-leaning
SaProt	LLR -6.74	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 4.1	GERP -0.92, phastCons 1
Regional constraint	o/e 1.44	unconstrained · MANE · 3,295 bp · p 6.5e-29 · regional, not allelic
Overall
CADD	17.84	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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: DRD4
Protein: p.Ser239Thr
Coding: c.716G>C
MANE Select: NM_000797
dbSNP: rs2133251867
Type: single nucleotide variant
Location: chr11:639965 (GRCh38)
Gene constraint: LOEUF 1.952 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 78.06 · 2 PDB
Residue 239: the 'disordered' region

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

Similar variants

DRD4 p.Ser239Arg Uncertain significance ★ ⚠ 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
DRD4 p.Pro248= 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-ser239thr (accessed [today's date]).

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