Is SETBP1 p.Pro559fs (c.1676del) pathogenic?

SETBP1 p.Pro559fs (c.1676del) is classified Pathogenic in SETBP1 (ClinVar, Single submitter, 1 submitter; last evaluated 2017-01-24). No gnomAD frequency available for this variant.

How common is SETBP1 p.Pro559fs (c.1676del) in the general population?

SETBP1 p.Pro559fs (c.1676del) is no gnomAD frequency available for this variant (gnomAD).

SETBP1 p.Pro559fs

c.1676del · rs1064796181 · VCV423032

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 haploinsufficient gene (ClinGen)
NMD	predicted	premature termination codon in exon 4 of 6
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP -0.062	GERP -5.4, phastCons 0.024

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: SETBP1
Protein: p.Pro559fs
Coding: c.1676del
MANE Select: NM_015559
dbSNP: rs1064796181
Type: Deletion
Location: chr18:44951012 (GRCh38)
Gene constraint: LOEUF 0.143 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 43.30

Full SETBP1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

SETBP1 p.Pro559= Benign/Likely benign ★★ same residue
SETBP1 p.Pro559Arg Uncertain significance ★ ⚠ same residue
SETBP1 p.Pro559Leu Uncertain significance ★ ⚠ same residue
SETBP1 p.Ala1071fs Pathogenic ★★ same type
SETBP1 p.Lys469_Met470insTer Pathogenic ★★ same type
SETBP1 p.Lys673fs Pathogenic/Likely pathogenic ★★ same type
SETBP1 p.Gln1575fs Uncertain significance ★★ same type
SETBP1 p.Leu1530_Pro1532del Likely benign ★★ 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/setbp1-p-pro559fs (accessed [today's date]).

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