Is FUS p.Thr64= (c.192A>G) pathogenic?

FUS p.Thr64= (c.192A>G) is classified Conflicting classifications of pathogenicity in FUS (ClinVar, Conflicting submitters, 5 submitters; last evaluated 2024-02-05). Very rare (popmax 0.00329%, sas); Associated with Inborn genetic diseases.

What condition is associated with FUS p.Thr64= (c.192A>G)?

FUS p.Thr64= (c.192A>G) is associated with Inborn genetic diseases, amyotrophic lateral sclerosis type 6, tremor, hereditary essential, 4 (ClinVar).

How common is FUS p.Thr64= (c.192A>G) in the general population?

FUS p.Thr64= (c.192A>G) is very rare (popmax 0.00329%, sas) (gnomAD).

FUS p.Thr64=

c.192A>G · rs776333956 · VCV318983

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 5 submitters

gnomAD v4.1

Rare

very rare (popmax 0.00329%, sas)

Conditions

Inborn genetic diseases

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation/SpliceAI carries the signal.
Splicing
SpliceAI	Δ0.99	acceptor loss, 2 bp away · masked 0 · deltas
Constraint at this position
Conservation	phyloP 8.1	GERP 2.2, phastCons 1
Overall
CADD	17.25	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00329% South Asian · 3/91,080 alleles

Filtering AF 0.000875% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000443%

Overall 0.000434% 7/1,614,064 alleles · very rare exomes 7/1,461,888 · genomes 0/152,176 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.00329%	30,360
Remaining individualsnot grpmax-eligible	0.0016%	62,512
European (non-Finnish)	0.000254%	393,337

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.Thr64=
Coding: c.192A>G
MANE Select: NM_004960
dbSNP: rs776333956
Type: single nucleotide variant
Location: chr16:31183859 (GRCh38)
Gene constraint: LOEUF 0.104 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 54.96 · 23 PDB
Residue 64: the 'disordered' region; a β-strand

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.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
FUS p.Lys510Glu 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-thr64 (accessed [today's date]).

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