Is EXOSC2 p.Pro8fs (c.23del) pathogenic?

EXOSC2 p.Pro8fs (c.23del) is classified Uncertain significance in EXOSC2 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-07-03). No gnomAD frequency available for this variant.

How common is EXOSC2 p.Pro8fs (c.23del) in the general population?

EXOSC2 p.Pro8fs (c.23del) is no gnomAD frequency available for this variant (gnomAD).

EXOSC2 p.Pro8fs

c.23del · rs2490767375 · VCV2013423

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Not reported

no gnomAD frequency available for this variant

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 1 of 9
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP -3.7	GERP -5.2

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

Population frequency

dbSNP / gnomAD

No gnomAD frequency available for this variant. 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: EXOSC2
Protein: p.Pro8fs
Coding: c.23del
MANE Select: NM_014285
dbSNP: rs2490767375
Type: Deletion
Location: chr9:130693813 (GRCh38)
Gene constraint: LOEUF 1.009 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 81.25 · 8 PDB
Residue 8: an α-helix

Full EXOSC2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

EXOSC2 p.Pro8Ala Benign/Likely benign ★★ same residue
EXOSC2 p.Pro8Leu Uncertain significance ★ ⚠ same residue
EXOSC2 p.Pro8Ser Uncertain significance ★ ⚠ same residue
EXOSC2 p.Pro8= Likely benign ★ same residue
EXOSC2 p.Arg287fs Uncertain significance ★★ same type
EXOSC2 p.Arg236fs Uncertain significance ★ same type
EXOSC2 p.Gln168fs Uncertain significance ★ same type
EXOSC2 p.Gly218fs Uncertain significance ★ same type

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/exosc2-p-pro8fs (accessed [today's date]).

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