Is DRD5 p.Ser395Phe (c.1184C>T) pathogenic?

DRD5 p.Ser395Phe (c.1184C>T) is classified Uncertain significance in DRD5 (ClinVar, Single submitter, 1 submitter; last evaluated 2016-02-13). AlphaMissense: likely benign (0.1787); Rare (popmax 0.15%, amr).

How common is DRD5 p.Ser395Phe (c.1184C>T) in the general population?

DRD5 p.Ser395Phe (c.1184C>T) is rare (popmax 0.15%, amr) (gnomAD).

What do computational predictors say about DRD5 p.Ser395Phe (c.1184C>T)?

AlphaMissense predicts likely benign (score 0.1787) — an in-silico prediction, not a clinical call.

DRD5 p.Ser395Phe

c.1184C>T · rs753296791 · VCV285972

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1787 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.15%, amr)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.1787	likely benign
REVEL	0.53	indeterminate
SaProt	LLR -8.09	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL makes no call.
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP 3.7	GERP -1.6, phastCons 1
Regional constraint	o/e 1.15	unconstrained · MANE · 1,430 bp · p 9.4e-05 · regional, not allelic
Overall
CADD	22.2	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 0.15% Admixed American · 90/60,012 alleles

Filtering AF 0.125% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.116%

Overall 0.0057% 92/1,614,094 alleles · rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.15%	667
Remaining individualsnot grpmax-eligible	0.0032%	31,245

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: DRD5
Protein: p.Ser395Phe
Coding: c.1184C>T
MANE Select: NM_020041 · reported on NM_000798
dbSNP: rs753296791
Type: single nucleotide variant
Location: chr4:9783213 (GRCh38)

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

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-ser395phe (accessed [today's date]).

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