Is DRD5 p.Leu88Phe (c.262C>T) pathogenic?

DRD5 p.Leu88Phe (c.262C>T) is classified Benign in DRD5 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2017-07-27). AlphaMissense: likely benign (0.1765); Rare (popmax 0.897%, nfe).

How common is DRD5 p.Leu88Phe (c.262C>T) in the general population?

DRD5 p.Leu88Phe (c.262C>T) is rare (popmax 0.897%, nfe) (gnomAD).

What do computational predictors say about DRD5 p.Leu88Phe (c.262C>T)?

AlphaMissense predicts likely benign (score 0.1765) — an in-silico prediction, not a clinical call.

DRD5 p.Leu88Phe

c.262C>T · rs148402761 · VCV592325

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

AlphaMissense

likely benign

0.1765 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.897%, nfe)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.1765	likely benign
REVEL	0.515	indeterminate
SaProt	LLR -7.70	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 4.6	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	25.5	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

Grpmax group 0.897% European (non-Finnish) · 10,582/1,179,882 alleles

Filtering AF 0.883% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.877%

Overall 0.727% 11,727/1,614,012 alleles · rare

Ancestry group	Frequency	1 in
Amishnot grpmax-eligible	1.1%	91
European (non-Finnish)grpmax	0.897%	111
Admixed American	0.76%	132
Remaining individualsnot grpmax-eligible	0.618%	162
Middle Eastern	0.182%	549
African / African-American	0.147%	682
South Asian	0.101%	990
Finnishnot grpmax-eligible	0.0906%	1,104
East Asian	0.0379%	2,640
Ashkenazi Jewishnot grpmax-eligible	0.0169%	5,921

Amish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Leu88Phe
Coding: c.262C>T
MANE Select: NM_000798
dbSNP: rs148402761
Type: single nucleotide variant
Location: chr4:9782291 (GRCh38)
Gene constraint: LOEUF 1.851 · pLI 0.09 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 69.45 · 1 PDB
Residue 88: a UniProt-annotated variant site (in); an α-helix

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 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
DRD5 p.Ala16Pro 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-leu88phe (accessed [today's date]).

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