Is FUS p.Arg386= (c.1156C>A) pathogenic?

FUS p.Arg386= (c.1156C>A) is classified Benign/Likely benign in FUS (ClinVar, Multiple submitters, 6 submitters; last evaluated 2026-02-02). Low-frequency (popmax 4.86%, afr); Associated with amyotrophic lateral sclerosis type 6.

What condition is associated with FUS p.Arg386= (c.1156C>A)?

FUS p.Arg386= (c.1156C>A) is associated with amyotrophic lateral sclerosis type 6, tremor, hereditary essential, 4 (ClinVar).

How common is FUS p.Arg386= (c.1156C>A) in the general population?

FUS p.Arg386= (c.1156C>A) is low-frequency (popmax 4.86%, afr) (gnomAD).

FUS p.Arg386=

Q: How is Frontotemporal dementia with motor neuron disease inherited?

Typically Autosomal dominant (Orphanet). A genetic counselor can assess individual risk for a family.

c.1156C>A · rs61733965 · VCV318990

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 6 submitters

gnomAD v4.1

Rare

low-frequency (popmax 4.86%, afr)

Conditions

amyotrophic lateral sclerosis type 6

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 4.1	GERP 1.9, phastCons 1
Overall
CADD	13.87	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 4.86% African / African-American · 3,639/74,926 alleles

Filtering AF 4.73% ClinGen BA1/BS1 input FAF95, joint · FAF99 4.67%

Overall 0.253% 4,078/1,613,930 alleles · low-frequency

Ancestry group	Frequency	1 in
African / African-Americangrpmax	4.86%	21
Admixed American	0.333%	300
Remaining individualsnot grpmax-eligible	0.317%	316
Middle Eastern	0.0992%	1,008
South Asian	0.00549%	18,214
European (non-Finnish)	0.00254%	39,333

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.Arg386=
Coding: c.1156C>A
MANE Select: NM_004960
dbSNP: rs61733965
Type: single nucleotide variant
Location: chr16:31190129 (GRCh38)
Gene constraint: LOEUF 0.104 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 54.96 · 23 PDB
Residue 386: a modified residue (asymmetric dimethylarginine); the 'disordered' region

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

Disease context

amyotrophic lateral sclerosis type 6 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: tremor, hereditary essential, 4

For Frontotemporal dementia with motor neuron disease (Orphanet):

Inheritance: Autosomal dominant
Onset: Adult

Similar variants

FUS p.Arg386Pro 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-arg386 (accessed [today's date]).

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