Is DRD2 p.Pro310Leu (c.929C>T) pathogenic?

DRD2 p.Pro310Leu (c.929C>T) is classified Uncertain significance in DRD2 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-01-23). AlphaMissense: likely benign (0.0752); Ultra-rare (popmax 0.02%, afr).

How common is DRD2 p.Pro310Leu (c.929C>T) in the general population?

DRD2 p.Pro310Leu (c.929C>T) is ultra-rare (popmax 0.02%, afr) (gnomAD).

What do computational predictors say about DRD2 p.Pro310Leu (c.929C>T)?

AlphaMissense predicts likely benign (score 0.0752) — an in-silico prediction, not a clinical call.

DRD2 p.Pro310Leu

c.929C>T · VCV3842451

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0752 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.02%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0752	likely benign
REVEL	0.061	moderately benign-leaning
SaProt	LLR -6.03	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · G>T here scores Δ0.22 · evaluated, not missing
Constraint at this position
Conservation	phyloP 8.4	GERP 1, phastCons 1
Regional constraint	o/e 0.93	unconstrained · MANE · 2,833 bp · p 0.35 · regional, not allelic
Overall
CADD	22.3	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

Grpmax group 0.02% African / African-American · 15/74,902 alleles

Filtering AF 0.0123% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00989%

Overall 0.00161% 26/1,613,680 alleles · ultra-rare exomes 20/1,461,530 · genomes 6/152,150 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.02%	4,993
Middle Eastern	0.0164%	6,084
Ashkenazi Jewishnot grpmax-eligible	0.00338%	29,602
Admixed American	0.00167%	59,998
South Asian	0.0011%	91,066
European (non-Finnish)	0.000593%	168,534

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.Pro310Leu
Coding: c.929C>T
MANE Select: NM_000795
Type: single nucleotide variant
Location: chr11:113412765 (GRCh38)
Gene constraint: LOEUF 0.372 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 72.49 · 11 PDB
Residue 310: 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

Similar variants

DRD2 p.Pro310Ser Conflicting classifications of pathogenicity ★ ⚠ same residue
DRD2 p.Pro310= Benign ★ same residue
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

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-pro310leu (accessed [today's date]).

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