Is EXOSC8 p.Pro87fs (c.259delinsTGG) pathogenic?

EXOSC8 p.Pro87fs (c.259delinsTGG) is classified Likely pathogenic in EXOSC8 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-02-04). Associated with pontocerebellar hypoplasia, type 1C.

What condition is associated with EXOSC8 p.Pro87fs (c.259delinsTGG)?

EXOSC8 p.Pro87fs (c.259delinsTGG) is associated with pontocerebellar hypoplasia, type 1C (ClinVar).

EXOSC8 p.Pro87fs

c.259delinsTGG · VCV4845689

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

Conditions

pontocerebellar hypoplasia, type 1C

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function
NMD	predicted	premature termination codon in exon 6 of 11
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 7.6	GERP 2.3, phastCons 1

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Variant & gene context

Gene: EXOSC8
Protein: p.Pro87fs
Coding: c.259delinsTGG
MANE Select: NM_181503
Type: Indel
Location: chr13:37005940 (GRCh38)
Gene constraint: LOEUF 1.944 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 85.77 · 8 PDB
Residue 87: a turn

Full EXOSC8 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

pontocerebellar hypoplasia, type 1C — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

EXOSC8 p.Pro87His Benign ★ same residue
EXOSC8 p.Asn180fs Uncertain significance ★★ same condition
EXOSC8 c.55-10_55-9del Benign/Likely benign ★★ same condition
EXOSC8 p.Gln107= Benign ★★ same condition
EXOSC8 c.17+1G>T Uncertain significance ★ same condition
EXOSC8 c.17+5del Uncertain significance ★ same condition
EXOSC8 p.Ala246fs Conflicting classifications of pathogenicity ★ same condition
EXOSC8 p.Arg23Cys 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/exosc8-p-pro87fs (accessed [today's date]).

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