Is DRD2 p.Lys327Glu (c.979A>G) pathogenic?

DRD2 p.Lys327Glu (c.979A>G) is classified Benign/Likely benign in DRD2 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2026-06-01). AlphaMissense: likely benign (0.1667); Rare (popmax 0.274%, nfe); Associated with dystonic disorder.

What condition is associated with DRD2 p.Lys327Glu (c.979A>G)?

DRD2 p.Lys327Glu (c.979A>G) is associated with dystonic disorder (ClinVar).

How common is DRD2 p.Lys327Glu (c.979A>G) in the general population?

DRD2 p.Lys327Glu (c.979A>G) is rare (popmax 0.274%, nfe) (gnomAD).

What do computational predictors say about DRD2 p.Lys327Glu (c.979A>G)?

AlphaMissense predicts likely benign (score 0.1667) — an in-silico prediction, not a clinical call.

DRD2 p.Lys327Glu

c.979A>G · rs71653614 · VCV238186

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

AlphaMissense

likely benign

0.1667 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.274%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

dystonic disorder

Computational evidence

Protein change
AlphaMissense	0.1667	likely benign
REVEL	0.212	benign-leaning
SaProt	LLR -6.05	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 7.9	GERP 2.2, phastCons 1
Regional constraint	o/e 0.93	unconstrained · MANE · 2,833 bp · p 0.35 · regional, not allelic
Overall
CADD	22.6	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 0.274% European (non-Finnish) · 3,232/1,180,052 alleles

Filtering AF 0.266% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.263%

Overall 0.312% 5,032/1,614,202 alleles · rare

Ancestry group	Frequency	1 in
Finnishnot grpmax-eligible	2.07%	48
Remaining individualsnot grpmax-eligible	0.286%	349
European (non-Finnish)grpmax	0.274%	365
South Asian	0.228%	438
Middle Eastern	0.0825%	1,212
African / African-American	0.0573%	1,745
Admixed American	0.0466%	2,144
Ashkenazi Jewishnot grpmax-eligible	0.0405%	2,467
East Asian	0.00223%	44,872

Finnish 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: DRD2
Protein: p.Lys327Glu
Coding: c.979A>G
MANE Select: NM_000795
dbSNP: rs71653614
Type: single nucleotide variant
Location: chr11:113412715 (GRCh38)
Gene constraint: LOEUF 0.372 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 72.49 · 11 PDB
Residue 327: the 'interaction with ppp1r9b' region; the 'disordered' region; a UniProt-annotated variant site (in)

Full DRD2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

dystonic disorder — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

DRD2 p.Arg274Gln Uncertain significance ★★ ⚠ same condition
DRD2 p.Gln366Lys Uncertain significance ★★ ⚠ same condition
DRD2 p.Glu99Lys Uncertain significance ★★ ⚠ same condition
DRD2 p.Gly261Arg Uncertain significance ★★ ⚠ same condition
DRD2 p.His316Pro Uncertain significance ★★ ⚠ same condition
DRD2 p.Ile431Thr Uncertain significance ★★ ⚠ same condition
DRD2 p.Pro300His Uncertain significance ★★ ⚠ same condition
DRD2 c.1139-653A>C 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/drd2-p-lys327glu (accessed [today's date]).

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