Is DRD1 p.Val430Ile (c.1288G>A) pathogenic?

DRD1 p.Val430Ile (c.1288G>A) is classified Uncertain significance in DRD1 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-09-10). AlphaMissense: likely benign (0.0734); Very rare (popmax 0.00068%, nfe).

How common is DRD1 p.Val430Ile (c.1288G>A) in the general population?

DRD1 p.Val430Ile (c.1288G>A) is very rare (popmax 0.00068%, nfe) (gnomAD).

What do computational predictors say about DRD1 p.Val430Ile (c.1288G>A)?

AlphaMissense predicts likely benign (score 0.0734) — an in-silico prediction, not a clinical call.

DRD1 p.Val430Ile

c.1288G>A · VCV4244778

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0734 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00068%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0734	likely benign
REVEL	0.163	moderately benign-leaning
SaProt	LLR -6.13	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 4.9	GERP 1.9, phastCons 1
Regional constraint	o/e 0.92	unconstrained · MANE · 298 bp · p 0.38 · regional, not allelic
Overall
CADD	17.68	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 0.00068% European (non-Finnish) · 8/1,176,252 alleles

Filtering AF 0.000293% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000211%

Overall 0.00055% 8/1,455,624 alleles · very rare

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: DRD1
Protein: p.Val430Ile
Coding: c.1288G>A
MANE Select: NM_000794
Type: single nucleotide variant
Location: chr5:175441812 (GRCh38)
Gene constraint: LOEUF 0.252 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 73.23 · 34 PDB

Full DRD1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

DRD1 c.-48G>A Likely benign ★★ same type
DRD1 p.Ala147Thr Uncertain significance ★ ⚠ same type
DRD1 p.Ala166Thr Uncertain significance ★ ⚠ same type
DRD1 p.Ala410Ser Uncertain significance ★ ⚠ same type
DRD1 p.Ala67Ser Uncertain significance ★ ⚠ same type
DRD1 p.Arg52Pro Uncertain significance ★ ⚠ same type
DRD1 p.Asn185Lys Uncertain significance ★ ⚠ same type
DRD1 p.Cys253Ser 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/drd1-p-val430ile (accessed [today's date]).

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