Is FUS p.Ser89= (c.267G>A) pathogenic?

FUS p.Ser89= (c.267G>A) is classified Likely benign in FUS (ClinVar, Multiple submitters, 2 submitters; last evaluated 2023-08-31). Ultra-rare (popmax 0.011%, sas); Associated with tremor, hereditary essential, 4.

What condition is associated with FUS p.Ser89= (c.267G>A)?

FUS p.Ser89= (c.267G>A) is associated with tremor, hereditary essential, 4, amyotrophic lateral sclerosis type 6 (ClinVar).

How common is FUS p.Ser89= (c.267G>A) in the general population?

FUS p.Ser89= (c.267G>A) is ultra-rare (popmax 0.011%, sas) (gnomAD).

FUS p.Ser89=

c.267G>A · rs761222382 · VCV1794669

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.011%, sas)

Conditions

tremor, hereditary essential, 4

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 -5.6	GERP -4.2
Overall
CADD	0.399	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.011% South Asian · 10/91,056 alleles

Filtering AF 0.00594% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00453%

Overall 0.00136% 22/1,613,882 alleles · ultra-rare exomes 22/1,461,618 · genomes 0/152,264 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.011%	9,106
Remaining individualsnot grpmax-eligible	0.0032%	31,252
East Asian	0.00223%	44,886
European (non-Finnish)	0.000763%	131,090

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.Ser89=
Coding: c.267G>A
MANE Select: NM_004960
dbSNP: rs761222382
Type: single nucleotide variant
Location: chr16:31183934 (GRCh38)
Gene constraint: LOEUF 0.104 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 54.96 · 23 PDB
Residue 89: the 'disordered' region

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

Disease context

tremor, hereditary essential, 4 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: amyotrophic lateral sclerosis type 6

Similar variants

FUS p.Ser89Thr 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
FUS p.Arg521His Pathogenic ★★ ⚠ same condition
FUS p.Arg521Leu Pathogenic/Likely 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-ser89 (accessed [today's date]).

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