Is FUS p.Gly228= (c.684C>T) pathogenic?

FUS p.Gly228= (c.684C>T) is classified Benign/Likely benign in FUS (ClinVar, Multiple submitters, 6 submitters; last evaluated 2026-04-01). Rare (popmax 0.706%, eas); Associated with Inborn genetic diseases.

What condition is associated with FUS p.Gly228= (c.684C>T)?

FUS p.Gly228= (c.684C>T) is associated with Inborn genetic diseases, amyotrophic lateral sclerosis type 6, tremor, hereditary essential, 4 (ClinVar).

How common is FUS p.Gly228= (c.684C>T) in the general population?

FUS p.Gly228= (c.684C>T) is rare (popmax 0.706%, eas) (gnomAD).

FUS p.Gly228=

c.684C>T · rs151073460 · VCV704135

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 6 submitters

gnomAD v4.1

Rare

rare (popmax 0.706%, 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 -0.68	GERP -4.1, phastCons 0.001
Overall
CADD	1.939	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.706% East Asian · 314/44,454 alleles

Filtering AF 0.642% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.617%

Overall 0.0397% 636/1,601,782 alleles · rare exomes 566/1,450,250 · genomes 70/151,532 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.706%	142
Remaining individualsnot grpmax-eligible	0.0452%	2,214
Middle Eastern	0.0331%	3,019
European (non-Finnish)	0.0229%	4,365
Admixed American	0.0139%	7,196
South Asian	0.0111%	9,016
African / African-American	0.00402%	24,883
Finnishnot grpmax-eligible	0.0032%	31,223

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.Gly228=
Coding: c.684C>T
MANE Select: NM_004960
dbSNP: rs151073460
Type: single nucleotide variant
Location: chr16:31185099 (GRCh38)
Gene constraint: LOEUF 0.104 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 54.96 · 23 PDB
Residue 228: 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.Gly228_Gly231del Uncertain significance ★★ same residue
FUS p.Gly228_Gly231dup 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

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-gly228 (accessed [today's date]).

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