Is PDE8B p.Phe705= (c.2115C>T) pathogenic?

PDE8B p.Phe705= (c.2115C>T) is classified Uncertain significance in PDE8B (ClinVar, Single submitter, 1 submitter; last evaluated 2018-01-13). Very rare (popmax 0.000339%, nfe); Associated with autosomal dominant striatal neurodegeneration type 1.

What condition is associated with PDE8B p.Phe705= (c.2115C>T)?

PDE8B p.Phe705= (c.2115C>T) is associated with autosomal dominant striatal neurodegeneration type 1 (ClinVar).

How common is PDE8B p.Phe705= (c.2115C>T) in the general population?

PDE8B p.Phe705= (c.2115C>T) is very rare (popmax 0.000339%, nfe) (gnomAD).

How is Autosomal dominant striatal neurodegeneration inherited?

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

PDE8B p.Phe705=

c.2115C>T · rs886060758 · VCV354167

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.000339%, nfe)

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 2.7	GERP 0.26, phastCons 1
Overall
CADD	11.92	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.000339% European (non-Finnish) · 4/1,179,240 alleles

Filtering AF 7.9e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 5.4e-05%

Overall 0.000248% 4/1,613,024 alleles · very rare exomes 4/1,460,708 · genomes 0/152,316 · joint denominator

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.Phe705=
Coding: c.2115C>T
MANE Select: NM_003719
dbSNP: rs886060758
Type: single nucleotide variant
Location: chr5:77418432 (GRCh38)
Gene constraint: LOEUF 0.351 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 74.88
Residue 705: the pdease domain

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-phe705 (accessed [today's date]).

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