Is FUS p.Tyr484= (c.1452C>T) pathogenic?

FUS p.Tyr484= (c.1452C>T) is classified Likely benign in FUS (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-08-30). Ultra-rare (popmax 0.0178%, eas); Associated with Inborn genetic diseases.

What condition is associated with FUS p.Tyr484= (c.1452C>T)?

FUS p.Tyr484= (c.1452C>T) is associated with Inborn genetic diseases, amyotrophic lateral sclerosis type 6, tremor, hereditary essential, 4 (ClinVar).

How common is FUS p.Tyr484= (c.1452C>T) in the general population?

FUS p.Tyr484= (c.1452C>T) is ultra-rare (popmax 0.0178%, eas) (gnomAD).

FUS p.Tyr484=

c.1452C>T · rs372721739 · VCV1137954

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0178%, eas)

Conditions

Inborn genetic diseases

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 2.3	GERP 0.013, phastCons 1
Overall
CADD	11.3	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0178% East Asian · 8/44,892 alleles

Filtering AF 0.00883% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00641%

Overall 0.00112% 18/1,613,732 alleles · ultra-rare exomes 15/1,461,672 · genomes 3/152,060 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.0178%	5,612
Remaining individualsnot grpmax-eligible	0.0128%	7,808
South Asian	0.0022%	45,521

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: FUS
Protein: p.Tyr484=
Coding: c.1452C>T
MANE Select: NM_004960
dbSNP: rs372721739
Type: single nucleotide variant
Location: chr16:31191021 (GRCh38)
Gene constraint: LOEUF 0.104 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 54.96 · 23 PDB
Residue 484: the 'disordered' region

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

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: amyotrophic lateral sclerosis type 6 tremor, hereditary essential, 4

Similar variants

FUS p.Tyr484Cys Uncertain significance ★ same residue
FUS p.Tyr484fs Pathogenic ★ same residue
FUS p.Tyr484_Arg485insHisAspArgGlyGlyTyr Uncertain significance ★ same residue
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

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-tyr484 (accessed [today's date]).

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