Is PDE8B p.Pro439= (c.1317G>A) pathogenic?

PDE8B p.Pro439= (c.1317G>A) is classified Likely benign in PDE8B (ClinVar, Multiple submitters, 2 submitters; last evaluated 2022-12-27). Ultra-rare (popmax 0.0111%, eas); Associated with autosomal dominant striatal neurodegeneration type 1.

What condition is associated with PDE8B p.Pro439= (c.1317G>A)?

PDE8B p.Pro439= (c.1317G>A) is associated with autosomal dominant striatal neurodegeneration type 1 (ClinVar).

How common is PDE8B p.Pro439= (c.1317G>A) in the general population?

PDE8B p.Pro439= (c.1317G>A) is ultra-rare (popmax 0.0111%, eas) (gnomAD).

How is Autosomal dominant striatal neurodegeneration inherited?

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

PDE8B p.Pro439=

c.1317G>A · rs754763694 · VCV354161

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0111%, eas)

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	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP -4.7	GERP -4.4
Overall
CADD	9.385	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0111% East Asian · 5/44,886 alleles

Filtering AF 0.00478% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00439%

Overall 0.00551% 89/1,613,936 alleles · ultra-rare exomes 83/1,461,760 · genomes 6/152,176 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.0111%	8,977
Ashkenazi Jewishnot grpmax-eligible	0.00676%	14,803
Remaining individualsnot grpmax-eligible	0.0064%	15,620
European (non-Finnish)	0.00593%	16,857
South Asian	0.00439%	22,771
African / African-American	0.004%	24,973
Admixed American	0.00167%	60,000

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.Pro439=
Coding: c.1317G>A
MANE Select: NM_003719
dbSNP: rs754763694
Type: single nucleotide variant
Location: chr5:77407409 (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 p.Pro439Gln 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-pro439 (accessed [today's date]).

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