Is DRD2 p.Thr357Ile (c.1070C>T) pathogenic?

DRD2 p.Thr357Ile (c.1070C>T) is classified Uncertain significance in DRD2 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-11-08). AlphaMissense: likely benign (0.233); Very rare (popmax 0.000254%, nfe).

How common is DRD2 p.Thr357Ile (c.1070C>T) in the general population?

DRD2 p.Thr357Ile (c.1070C>T) is very rare (popmax 0.000254%, nfe) (gnomAD).

What do computational predictors say about DRD2 p.Thr357Ile (c.1070C>T)?

AlphaMissense predicts likely benign (score 0.233) — an in-silico prediction, not a clinical call.

DRD2 p.Thr357Ile

c.1070C>T · VCV3505229

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.233 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000254%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.233	likely benign
REVEL	0.185	benign-leaning
SaProt	LLR -7.52	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 5.8	GERP 1.2, phastCons 1
Regional constraint	o/e 0.49	unconstrained · MANE · 1,939 bp · p 3.2e-09 · regional, not allelic
Overall
CADD	19.64	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 0.000254% European (non-Finnish) · 3/1,180,058 alleles

Filtering AF 6.8e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.9e-05%

Overall 0.000248% 4/1,614,102 alleles · very rare

Ancestry group	Frequency	1 in
Ashkenazi Jewishnot grpmax-eligible	0.00338%	29,606
European (non-Finnish)grpmax	0.000254%	393,352

Ashkenazi Jewish 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.Thr357Ile
Coding: c.1070C>T
MANE Select: NM_000795
Type: single nucleotide variant
Location: chr11:113412624 (GRCh38)
Gene constraint: LOEUF 0.372 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 72.49 · 11 PDB
Residue 357: 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-thr357ile (accessed [today's date]).

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