Is PDE8B p.Ala52= (c.156C>T) pathogenic?

PDE8B p.Ala52= (c.156C>T) is classified Conflicting classifications of pathogenicity in PDE8B (ClinVar, Conflicting submitters, 2 submitters; last evaluated 2025-10-22). Ultra-rare (popmax 0.0535%, amr); Associated with autosomal dominant striatal neurodegeneration type 1.

What condition is associated with PDE8B p.Ala52= (c.156C>T)?

PDE8B p.Ala52= (c.156C>T) is associated with autosomal dominant striatal neurodegeneration type 1 (ClinVar).

How common is PDE8B p.Ala52= (c.156C>T) in the general population?

PDE8B p.Ala52= (c.156C>T) is ultra-rare (popmax 0.0535%, amr) (gnomAD).

How is Autosomal dominant striatal neurodegeneration inherited?

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

PDE8B p.Ala52=

c.156C>T · rs886060755 · VCV354147

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0535%, amr)

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 2.6	GERP 1.1, phastCons 0.99
Overall
CADD	14.89	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0535% Admixed American · 25/46,706 alleles

Filtering AF 0.0372% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0318%

Overall 0.0022% 33/1,500,380 alleles · ultra-rare exomes 14/1,348,342 · genomes 19/152,038 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.0535%	1,868
Remaining individualsnot grpmax-eligible	0.0103%	9,703
African / African-American	0.00145%	69,184
South Asian	0.00124%	80,542

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: PDE8B
Protein: p.Ala52=
Coding: c.156C>T
MANE Select: NM_003719
dbSNP: rs886060755
Type: single nucleotide variant
Location: chr5:77211081 (GRCh38)
Gene constraint: LOEUF 0.351 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 74.88

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 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
PDE8B p.Val45Leu 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-ala52 (accessed [today's date]).

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