Is FUS p.Phe506fs (c.1510_1514dup) pathogenic?

FUS p.Phe506fs (c.15101514dup) is classified Pathogenic in FUS (ClinVar, Single submitter, 1 submitter; last evaluated 2016-05-13). Absent from gnomAD.

How common is FUS p.Phe506fs (c.1510_1514dup) in the general population?

FUS p.Phe506fs (c.1510_1514dup) is absent from gnomAD (gnomAD).

FUS p.Phe506fs

c.1510_1514dup · rs886041776 · VCV280602

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Not reported

no gnomAD frequency available for this variant

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function in a LoF-intolerant gene
NMD	escapes	premature termination codon within the last 50 nt of the penultimate exon (14 of 15, 32 nt from its 3' end) — the truncated protein is likely expressed. PVS1 input, not an applied code
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 11	GERP 2.2, phastCons 1

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

dbSNP / gnomAD

No gnomAD frequency available for this variant. This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: FUS
Protein: p.Phe506fs
Coding: c.1510_1514dup
MANE Select: NM_004960
dbSNP: rs886041776
Type: Duplication
Location: chr16:31191078 (GRCh38)
Gene constraint: LOEUF 0.104 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 54.96 · 23 PDB
Residue 506: the 'disordered' region

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

Similar variants

FUS p.Gly247_Arg248insGly Uncertain significance ★★ same type
FUS p.Gly458_Pro459insGly Uncertain significance ★★ same type
FUS c.524-13dup Benign/Likely benign ★★ same type
FUS p.Arg495fs Likely pathogenic ★ same type
FUS p.Arg498fs Likely pathogenic ★ same type
FUS p.Gly465fs Pathogenic ★ same type
FUS p.Gly500fs Likely pathogenic ★ same type
FUS p.Gly501fs 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-phe506fs (accessed [today's date]).

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