Is DRD5 p.Cys375Ser (c.1123T>A) pathogenic?

DRD5 p.Cys375Ser (c.1123T>A) is classified Uncertain significance in DRD5 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-02-07). AlphaMissense: likely benign (0.219); Absent from gnomAD v4.1.

How common is DRD5 p.Cys375Ser (c.1123T>A) in the general population?

DRD5 p.Cys375Ser (c.1123T>A) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about DRD5 p.Cys375Ser (c.1123T>A)?

AlphaMissense predicts likely benign (score 0.219) — an in-silico prediction, not a clinical call.

DRD5 p.Cys375Ser

c.1123T>A · rs2474579235 · VCV2480667

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.219 · 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	0.219	likely benign
REVEL	0.33	indeterminate
SaProt	LLR -8.58	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 4.8	GERP 1.8, phastCons 1
Regional constraint	o/e 1.15	unconstrained · MANE · 1,430 bp · p 9.4e-05 · regional, not allelic
Overall
CADD	23.9	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: DRD5
Protein: p.Cys375Ser
Coding: c.1123T>A
MANE Select: NM_000798
dbSNP: rs2474579235
Type: single nucleotide variant
Location: chr4:9783152 (GRCh38)
Gene constraint: LOEUF 1.851 · pLI 0.09 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 69.45 · 1 PDB

Full DRD5 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

DRD5 p.Val59Met Uncertain significance ★★ ⚠ same type
DRD5 c.-226G>C Benign ★★ same type
DRD5 c.*178G>T Benign ★★ same type
DRD5 p.Leu88Phe Benign ★★ ⚠ same type
DRD5 c.*47T>C Conflicting classifications of pathogenicity ★ same type
DRD5 p.Ala10Val Uncertain significance ★ ⚠ same type
DRD5 p.Ala111Glu Uncertain significance ★ ⚠ same type
DRD5 p.Ala164Glu 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/drd5-p-cys375ser (accessed [today's date]).

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