Is DRD2 c.285+91A>T pathogenic?

DRD2 c.285+91A>T is classified Benign in DRD2 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2021-06-18). Common (popmax 60.7%, nfe) — too common for a highly-penetrant pathogenic allele.

DRD2 c.285+91A>T

Q: How common is DRD2 c.285+91A>T in the general population?

DRD2 c.285+91A>T is common (popmax 60.7%, nfe) — too common for a highly-penetrant pathogenic allele (gnomAD).

rs12808482 · VCV1289649

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Common

common (popmax 60.7%, nfe) — too common for a highly-penetrant pathogenic allele

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
Splice region	donor +91	deep intronic (+91 nt into the intron)
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -0.94	GERP -2.8
Non-coding constraint	Z 2.71	1 kb window · o/e 0.69 · regional · uncalibrated
Overall
CADD	1.493	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 60.7% European (non-Finnish) · 630,529/1,038,612 alleles

Filtering AF 60.6% ClinGen BA1/BS1 input FAF95, joint · FAF99 60.5%

Overall 54.5% 779,134/1,430,594 alleles · common

Ancestry group	Frequency	1 in
Amishnot grpmax-eligible	70.9%	1
Ashkenazi Jewishnot grpmax-eligible	65.1%	2
European (non-Finnish)grpmax	60.7%	2
Middle Eastern	55.8%	2
Remaining individualsnot grpmax-eligible	53.1%	2
Finnishnot grpmax-eligible	49.9%	2
South Asian	39.9%	3
Admixed American	34.4%	3
African / African-American	22%	5
East Asian	6.02%	17

Amish 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
Coding: c.285+91A>T
MANE Select: NM_000795
dbSNP: rs12808482
Type: single nucleotide variant
Location: chr11:113424276 (GRCh38)
Gene constraint: LOEUF 0.372 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 72.49 · 11 PDB

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-c-285-plus-91a-t (accessed [today's date]).

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