Is DRD2 p.Cys244Ser (c.731G>C) pathogenic?

DRD2 p.Cys244Ser (c.731G>C) is classified Uncertain significance in DRD2 (ClinVar, Single submitter, 1 submitter; last evaluated 2015-05-22). AlphaMissense: likely pathogenic (0.57); Very rare (popmax 0.0011%, sas).

How common is DRD2 p.Cys244Ser (c.731G>C) in the general population?

DRD2 p.Cys244Ser (c.731G>C) is very rare (popmax 0.0011%, sas) (gnomAD).

What do computational predictors say about DRD2 p.Cys244Ser (c.731G>C)?

AlphaMissense predicts likely pathogenic (score 0.57) — an in-silico prediction, not a clinical call.

DRD2 p.Cys244Ser

c.731G>C · rs794727782 · VCV198103

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.57 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.0011%, sas)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.57	likely pathogenic
REVEL	0.301	indeterminate
SaProt	LLR -3.62	tolerated
⇒ AlphaMissense calls this damaging; SaProt does not; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 1.8	GERP -1.4, phastCons 0.94
Regional constraint	o/e 0.93	unconstrained · MANE · 2,833 bp · p 0.35 · regional, not allelic
Overall
CADD	19.64	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 0.0011% South Asian · 1/91,088 alleles

Overall 6.2e-05% 1/1,614,168 alleles · very rare exomes 1/1,461,888 · genomes 0/152,280 · joint denominator

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.Cys244Ser
Coding: c.731G>C
MANE Select: NM_000795
dbSNP: rs794727782
Type: single nucleotide variant
Location: chr11:113414454 (GRCh38)
Gene constraint: LOEUF 0.372 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 72.49 · 11 PDB
Residue 244: the 'interaction with ppp1r9b' region

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

Similar variants

DRD2 p.Arg274Gln Uncertain significance ★★ ⚠ same type
DRD2 p.Gln366Lys Uncertain significance ★★ ⚠ same type
DRD2 p.Glu99Lys Uncertain significance ★★ ⚠ same type
DRD2 p.Gly261Arg Uncertain significance ★★ ⚠ same type
DRD2 p.His316Pro Uncertain significance ★★ ⚠ same type
DRD2 p.Ile431Thr Uncertain significance ★★ ⚠ same type
DRD2 p.Pro300His Uncertain significance ★★ ⚠ same type
DRD2 p.Val223Ile Uncertain significance ★★ ⚠ 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/drd2-p-cys244ser (accessed [today's date]).

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