Is FUS p.Arg473His (c.1418G>A) pathogenic?

FUS p.Arg473His (c.1418G>A) is classified Uncertain significance in FUS (ClinVar, Single submitter, 1 submitter; last evaluated 2026-03-23). AlphaMissense: ambiguous (0.4905); Very rare (popmax 0.0022%, sas); Associated with Inborn genetic diseases.

What condition is associated with FUS p.Arg473His (c.1418G>A)?

FUS p.Arg473His (c.1418G>A) is associated with Inborn genetic diseases (ClinVar).

How common is FUS p.Arg473His (c.1418G>A) in the general population?

FUS p.Arg473His (c.1418G>A) is very rare (popmax 0.0022%, sas) (gnomAD).

What do computational predictors say about FUS p.Arg473His (c.1418G>A)?

AlphaMissense predicts ambiguous (score 0.4905) — an in-silico prediction, not a clinical call.

FUS p.Arg473His

c.1418G>A · rs777102516 · VCV1772177

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.4905 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.0022%, sas)

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.4905	ambiguous
REVEL	0.291	indeterminate
SaProt	LLR -10.34	damaging
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 8.8	GERP -0.12, phastCons 1
Regional constraint	o/e 0.80	unconstrained · MANE · 644 bp · p 0.025 · regional, not allelic
Overall
CADD	25.6	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0022% South Asian · 2/91,046 alleles

Filtering AF 0.000365% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000137%

Overall 0.000342% 5/1,461,338 alleles · very rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0022%	45,523
European (non-Finnish)	0.000254%	393,221

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.Arg473His
Coding: c.1418G>A
MANE Select: NM_004960
dbSNP: rs777102516
Type: single nucleotide variant
Location: chr16:31190987 (GRCh38)
Gene constraint: LOEUF 0.104 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 54.96 · 23 PDB
Residue 473: a modified residue (asymmetric dimethylarginine); 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

Similar variants

FUS p.Arg473Cys Uncertain significance ★ ⚠ same residue
FUS c.833-6A>G Uncertain significance ★★ same condition
FUS p.Arg269Trp Uncertain significance ★★ ⚠ same condition
FUS p.Arg472Cys Uncertain significance ★★ ⚠ same condition
FUS p.Arg498Gln Uncertain significance ★★ same condition
FUS p.Gln199Glu Uncertain significance ★★ ⚠ same condition
FUS p.Gly515Ser Uncertain significance ★★ ⚠ same condition
FUS p.Pro152Ser Uncertain significance ★★ ⚠ 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-arg473his (accessed [today's date]).

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