Is TSEN2 p.Phe306fs (c.917del) pathogenic?

TSEN2 p.Phe306fs (c.917del) is classified Pathogenic in TSEN2 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-11-25). Associated with pontocerebellar hypoplasia.

What condition is associated with TSEN2 p.Phe306fs (c.917del)?

TSEN2 p.Phe306fs (c.917del) is associated with pontocerebellar hypoplasia (ClinVar).

TSEN2 p.Phe306fs

c.917del · VCV3658805

Pathogenic Multiple submitters

Classification

Pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

Conditions

pontocerebellar hypoplasia

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 7 of 12
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP -0.66	GERP -4.2, phastCons 0.009

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

Variant & gene context

Gene: TSEN2
Protein: p.Phe306fs
Coding: c.917del
MANE Select: NM_025265
Type: Deletion
Location: chr3:12516614 (GRCh38)
Gene constraint: LOEUF 1.212 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 73.63 · 5 PDB
Residue 306: an α-helix

Full TSEN2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

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

Similar variants

TSEN2 c.960+1_960+5del Likely pathogenic ★★ same condition
TSEN2 p.Gln118fs Likely pathogenic ★★ same condition
TSEN2 c.1099+1G>A Likely pathogenic ★★ same condition
TSEN2 p.Tyr19Ter Pathogenic/Likely pathogenic ★★ same condition
TSEN2 p.Ala227Val Uncertain significance ★★ ⚠ same condition
TSEN2 p.Asn282Ser Uncertain significance ★★ ⚠ same condition
TSEN2 p.Asp250Asn Uncertain significance ★★ ⚠ same condition
TSEN2 p.Glu212Ala 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/tsen2-p-phe306fs (accessed [today's date]).

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