Is FUS p.Arg524Ser (c.1572G>C) pathogenic?

FUS p.Arg524Ser (c.1572G>C) is classified Pathogenic in FUS (ClinVar, Single submitter, 1 submitter; last evaluated 2016-08-31). AlphaMissense: likely pathogenic (0.9979); Absent from gnomAD v4.1.

How common is FUS p.Arg524Ser (c.1572G>C) in the general population?

FUS p.Arg524Ser (c.1572G>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about FUS p.Arg524Ser (c.1572G>C)?

AlphaMissense predicts likely pathogenic (score 0.9979) — an in-silico prediction, not a clinical call.

FUS p.Arg524Ser

c.1572G>C · rs886041389 · VCV280109

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9979 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.9979	likely pathogenic ✓ concordant with ClinVar
REVEL	0.673	pathogenic-leaning
SaProt	LLR -8.75	tolerated
⇒ AlphaMissense and REVEL call this damaging; SaProt does not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 5.8	GERP 0.89, phastCons 1
Regional constraint	o/e 0.80	unconstrained · MANE · 644 bp · p 0.025 · regional, not allelic
Overall
CADD	24.7	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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: FUS
Protein: p.Arg524Ser
Coding: c.1572G>C
MANE Select: NM_004960
dbSNP: rs886041389
Type: single nucleotide variant
Location: chr16:31191429 (GRCh38)
Gene constraint: LOEUF 0.104 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 54.96 · 23 PDB
Residue 524: the 'disordered' region; a UniProt-annotated variant site (in als6)

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

Similar variants

FUS p.Arg524Met Likely pathogenic ★ same residue
FUS p.Arg524Trp Uncertain significance ★ ⚠ same residue
FUS p.Arg481Ter Pathogenic/Likely pathogenic ★★ same type
FUS p.Arg495Ter Pathogenic ★★ same type
FUS p.Arg514Gly Pathogenic ★★ ⚠ same type
FUS p.Arg521Cys Pathogenic ★★ same type
FUS p.Arg521Gly Pathogenic ★★ same type
FUS p.Arg521His Pathogenic ★★ ⚠ same type

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-arg524ser (accessed [today's date]).

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