Is PDE8B p.Arg18= (c.52C>A) pathogenic?

PDE8B p.Arg18= (c.52C>A) is classified Uncertain significance in PDE8B (ClinVar, Single submitter, 1 submitter; last evaluated 2018-01-13). No allele count reported in gnomAD v4.1 (AN 1,538,758); Associated with autosomal dominant striatal neurodegeneration type 1.

What condition is associated with PDE8B p.Arg18= (c.52C>A)?

PDE8B p.Arg18= (c.52C>A) is associated with autosomal dominant striatal neurodegeneration type 1 (ClinVar).

How common is PDE8B p.Arg18= (c.52C>A) in the general population?

PDE8B p.Arg18= (c.52C>A) is no allele count reported in gnomAD v4.1 (AN 1,538,758) (gnomAD).

How is Autosomal dominant striatal neurodegeneration inherited?

Typically Autosomal dominant (Orphanet). A genetic counselor can assess individual risk for a family.

PDE8B p.Arg18=

c.52C>A · rs886060753 · VCV354144

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 1,538,758)

Conditions

autosomal dominant striatal neurodegeneration type 1

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 4.1	GERP 0.21, phastCons 1
Overall
CADD	14.63	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

No allele count reported in gnomAD v4.1 (AN 1,538,758). This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: PDE8B
Protein: p.Arg18=
Coding: c.52C>A
MANE Select: NM_003719
dbSNP: rs886060753
Type: single nucleotide variant
Location: chr5:77210977 (GRCh38)
Gene constraint: LOEUF 0.351 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 74.88
Residue 18: the 'disordered' region

Full PDE8B gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

autosomal dominant striatal neurodegeneration type 1 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Autosomal dominant striatal neurodegeneration (Orphanet):

Inheritance: Autosomal dominant
Onset: Adult

Similar variants

PDE8B p.Arg18Pro Uncertain significance ★ ⚠ same residue
PDE8B c.*498C>A Uncertain significance ★★ same condition
PDE8B p.Arg483Trp Uncertain significance ★★ ⚠ same condition
PDE8B p.Arg94Gly Uncertain significance ★★ ⚠ same condition
PDE8B p.Asp849Asn Uncertain significance ★★ same condition
PDE8B p.Cys334Tyr Uncertain significance ★★ ⚠ same condition
PDE8B p.Gly42Ala Uncertain significance ★★ ⚠ same condition
PDE8B p.Ser611Ala Uncertain significance ★★ ⚠ same condition

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/pde8b-p-arg18 (accessed [today's date]).

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