Is FUS p.Asp283= (c.849C>T) pathogenic?

FUS p.Asp283= (c.849C>T) is classified Likely benign in FUS (ClinVar, Single submitter, 1 submitter; last evaluated 2022-03-14). Very rare (popmax 0.00333%, amr); Associated with tremor, hereditary essential, 4.

What condition is associated with FUS p.Asp283= (c.849C>T)?

FUS p.Asp283= (c.849C>T) is associated with tremor, hereditary essential, 4, amyotrophic lateral sclerosis type 6 (ClinVar).

How common is FUS p.Asp283= (c.849C>T) in the general population?

FUS p.Asp283= (c.849C>T) is very rare (popmax 0.00333%, amr) (gnomAD).

FUS p.Asp283=

c.849C>T · rs192350464 · VCV2047719

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00333%, amr)

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
Pangolin	Δ0.24	loss · gain 0.01 · not in the SpliceAI release · independent
Constraint at this position
Conservation	phyloP 2.2	GERP 2, phastCons 1
Overall
CADD	12.27	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00333% Admixed American · 2/60,014 alleles

Filtering AF 0.000553% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000207%

Overall 0.000434% 7/1,613,490 alleles · very rare exomes 6/1,461,222 · genomes 1/152,268 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00333%	30,007
European (non-Finnish)	0.000424%	235,884

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.Asp283=
Coding: c.849C>T
MANE Select: NM_004960
dbSNP: rs192350464
Type: single nucleotide variant
Location: chr16:31189139 (GRCh38)
Gene constraint: LOEUF 0.104 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 54.96 · 23 PDB
Residue 283: 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.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-asp283 (accessed [today's date]).

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