Is FUS p.Pro98Thr (c.291_292delinsTA) pathogenic?

FUS p.Pro98Thr (c.291292delinsTA) is classified Uncertain significance in FUS (ClinVar, Single submitter, 1 submitter; last evaluated 2019-11-25). Absent from gnomAD; Associated with amyotrophic lateral sclerosis type 6.

What condition is associated with FUS p.Pro98Thr (c.291_292delinsTA)?

FUS p.Pro98Thr (c.291_292delinsTA) is associated with amyotrophic lateral sclerosis type 6, tremor, hereditary essential, 4 (ClinVar).

How common is FUS p.Pro98Thr (c.291_292delinsTA) in the general population?

FUS p.Pro98Thr (c.291_292delinsTA) is absent from gnomAD (gnomAD).

FUS p.Pro98Thr

Q: How is Frontotemporal dementia with motor neuron disease inherited?

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

c.291_292delinsTA · rs2079220021 · VCV838008

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Not reported

no gnomAD frequency available for this variant

Conditions

amyotrophic lateral sclerosis type 6

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP -0.39	GERP -4.3, phastCons 0.13
Regional constraint	o/e 0.91	unconstrained · MANE · 4,906 bp · p 0.12 · regional, not allelic

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: FUS
Protein: p.Pro98Thr
Coding: c.291_292delinsTA
MANE Select: NM_004960
dbSNP: rs2079220021
Type: Indel
Location: chr16:31183958 (GRCh38)
Gene constraint: LOEUF 0.104 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 54.96 · 23 PDB
Residue 98: the 'disordered' region; a turn

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

Disease context

amyotrophic lateral sclerosis type 6 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: tremor, hereditary essential, 4

For Frontotemporal dementia with motor neuron disease (Orphanet):

Inheritance: Autosomal dominant
Onset: Adult

Similar variants

FUS p.Pro98Leu Uncertain significance ★ same residue
FUS c.1394-2del Pathogenic/Likely pathogenic ★★ same condition
FUS p.Arg481Ter Pathogenic/Likely pathogenic ★★ same condition
FUS p.Arg495Ter Pathogenic ★★ same condition
FUS p.Arg514Gly Pathogenic ★★ ⚠ same condition
FUS p.Arg521Cys Pathogenic ★★ same condition
FUS p.Arg521Gly Pathogenic ★★ same condition
FUS p.Arg521His Pathogenic ★★ ⚠ 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/fus-p-pro98thr (accessed [today's date]).

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