Is SETBP1 p.Pro185fs (c.550_551dup) pathogenic?

SETBP1 p.Pro185fs (c.550551dup) is classified Likely pathogenic in SETBP1 (ClinVar, Single submitter, 1 submitter; last evaluated 2021-04-22). Associated with SETBP1-related disorder.

What condition is associated with SETBP1 p.Pro185fs (c.550_551dup)?

SETBP1 p.Pro185fs (c.550_551dup) is associated with SETBP1-related disorder (ClinVar).

SETBP1 p.Pro185fs

c.550_551dup · VCV4938846

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

Conditions

SETBP1-related disorder

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 -6.4	GERP -5.3

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

Variant & gene context

Gene: SETBP1
Protein: p.Pro185fs
Coding: c.550_551dup
MANE Select: NM_015559
Type: Microsatellite
Location: chr18:44949886 (GRCh38)
Gene constraint: LOEUF 0.143 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 43.30
Residue 185: the 'disordered' region

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

Disease context

SETBP1-related disorder

Similar variants

SETBP1 p.Pro185Ser Uncertain significance ★★ ⚠ same residue
SETBP1 p.Pro185= Likely benign ★ same residue
SETBP1 c.540+7417TC[5] Likely pathogenic same condition
SETBP1 p.Ala1071fs Pathogenic ★★ same condition
SETBP1 p.Arg544Ter Pathogenic/Likely pathogenic ★★ same condition
SETBP1 p.Arg626Ter Pathogenic ★★ same condition
SETBP1 p.Asp868Asn Pathogenic ★★ ⚠ same condition
SETBP1 p.Ser867Arg 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/setbp1-p-pro185fs (accessed [today's date]).

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