Is DRD4 p.Pro297Ala (c.889C>G) pathogenic?

DRD4 p.Pro297Ala (c.889C>G) is classified Likely benign in DRD4 (ClinVar, Single submitter, 3 submitters). AlphaMissense: likely benign (0.0519); Ultra-rare (popmax 0.0665%, eas).

How common is DRD4 p.Pro297Ala (c.889C>G) in the general population?

DRD4 p.Pro297Ala (c.889C>G) is ultra-rare (popmax 0.0665%, eas) (gnomAD).

What do computational predictors say about DRD4 p.Pro297Ala (c.889C>G)?

AlphaMissense predicts likely benign (score 0.0519) — an in-silico prediction, not a clinical call.

DRD4 p.Pro297Ala

c.889C>G · rs1365230157 · VCV1206105

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 3 submitters

AlphaMissense

likely benign

0.0519 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0665%, eas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0519	likely benign
REVEL	0.163	moderately benign-leaning
SaProt	LLR -5.95	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 -3	GERP -0.25
Regional constraint	o/e 1.44	unconstrained · MANE · 3,295 bp · p 6.5e-29 · regional, not allelic
Overall
CADD	2.477	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 0.0665% East Asian · 25/37,578 alleles

Filtering AF 0.0462% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0395%

Overall 0.0255% 368/1,442,616 alleles · ultra-rare exomes 341/1,293,152 · genomes 27/149,464 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.0665%	1,503
African / African-American	0.0426%	2,347
Admixed American	0.0305%	3,282
Finnishnot grpmax-eligible	0.0275%	3,630
Middle Eastern	0.0247%	4,050
European (non-Finnish)	0.0241%	4,145
Remaining individualsnot grpmax-eligible	0.0232%	4,317
South Asian	0.0161%	6,202

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: DRD4
Protein: p.Pro297Ala
Coding: c.889C>G
MANE Select: NM_000797
dbSNP: rs1365230157
Type: single nucleotide variant
Location: chr11:640138 (GRCh38)
Gene constraint: LOEUF 1.952 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 78.06 · 2 PDB
Residue 297: the '4 x 16 aa approximate tandem repeats of [pa]-a-p-g-l-p-[pqr]-[dg]-p-c-g-p-d-c-a-p' region

Full DRD4 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

DRD4 p.Pro297Leu Uncertain significance ★ ⚠ same residue
DRD4 p.Asn309Asp Uncertain significance ★★ ⚠ same type
DRD4 p.Ser308Pro Uncertain significance ★★ ⚠ same type
DRD4 p.Ala335Gly Benign ★★ same type
DRD4 p.Gly11Arg Benign ★★ same type
DRD4 p.Leu83= Likely benign ★★ same type
DRD4 p.Pro244= Likely benign ★★ same type
DRD4 p.Pro248= Likely benign ★★ 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/drd4-p-pro297ala (accessed [today's date]).

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