Is DRD1 p.Ser263Pro (c.787T>C) pathogenic?

DRD1 p.Ser263Pro (c.787T>C) is classified Uncertain significance in DRD1 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-05-13). AlphaMissense: likely pathogenic (0.831); Absent from gnomAD v4.1.

How common is DRD1 p.Ser263Pro (c.787T>C) in the general population?

DRD1 p.Ser263Pro (c.787T>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about DRD1 p.Ser263Pro (c.787T>C)?

AlphaMissense predicts likely pathogenic (score 0.831) — an in-silico prediction, not a clinical call.

DRD1 p.Ser263Pro

c.787T>C · VCV4014828

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.831 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.831	likely pathogenic
REVEL	0.593	indeterminate
SaProt	LLR -8.27	tolerated
⇒ AlphaMissense calls this damaging; SaProt does not; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 9.4	GERP 1.9, phastCons 1
Regional constraint	o/e 0.44	unconstrained · MANE · 269 bp · p 7.6e-09 · regional, not allelic
Overall
CADD	28.9	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

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.Ser263Pro
Coding: c.787T>C
MANE Select: NM_000794
Type: single nucleotide variant
Location: chr5:175442313 (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-ser263pro (accessed [today's date]).

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