Is DRD1 p.Ile308Met (c.924T>G) pathogenic?

DRD1 p.Ile308Met (c.924T>G) is classified Uncertain significance in DRD1 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-06-24). AlphaMissense: likely benign (0.1307); Absent from gnomAD v4.1.

How common is DRD1 p.Ile308Met (c.924T>G) in the general population?

DRD1 p.Ile308Met (c.924T>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about DRD1 p.Ile308Met (c.924T>G)?

AlphaMissense predicts likely benign (score 0.1307) — an in-silico prediction, not a clinical call.

DRD1 p.Ile308Met

c.924T>G · VCV4244772

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1307 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.1307	likely benign
REVEL	0.491	indeterminate
SaProt	LLR -9.46	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -6.8	GERP -3.5
Regional constraint	o/e 0.44	unconstrained · MANE · 269 bp · p 7.6e-09 · regional, not allelic
Overall
CADD	2.714	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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: DRD1
Protein: p.Ile308Met
Coding: c.924T>G
MANE Select: NM_000794
Type: single nucleotide variant
Location: chr5:175442176 (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-ile308met (accessed [today's date]).

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