Is SETBP1 p.Ser238fs (c.712del) pathogenic?

SETBP1 p.Ser238fs (c.712del) is classified Pathogenic in SETBP1 (ClinVar, Single submitter, 1 submitter). Associated with intellectual disability, autosomal dominant 29.

What condition is associated with SETBP1 p.Ser238fs (c.712del)?

SETBP1 p.Ser238fs (c.712del) is associated with intellectual disability, autosomal dominant 29, Schinzel-Giedion syndrome (ClinVar).

How is Non-specific syndromic intellectual disability inherited?

Typically Autosomal dominant, Autosomal recessive (Orphanet). A genetic counselor can assess individual risk for a family.

SETBP1 p.Ser238fs

c.712del · VCV4533245

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

Conditions

intellectual disability, autosomal dominant 29

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 2.7	GERP 0.88, phastCons 1

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

Variant & gene context

Gene: SETBP1
Protein: p.Ser238fs
Coding: c.712del
MANE Select: NM_015559
Type: Deletion
Location: chr18:44950052 (GRCh38)
Gene constraint: LOEUF 0.143 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 43.30
Residue 238: the 'disordered' region

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

Disease context

intellectual disability, autosomal dominant 29 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: Schinzel-Giedion syndrome

For Non-specific syndromic intellectual disability (Orphanet):

Inheritance: Autosomal dominant, Autosomal recessive, X-linked recessive
Onset: Childhood, Infancy

Similar variants

SETBP1 p.Lys469_Met470insTer Pathogenic ★★ same condition
SETBP1 p.Ala374fs Pathogenic ★ same condition
SETBP1 p.Arg112fs Pathogenic ★ same condition
SETBP1 p.Arg421fs Likely pathogenic ★ same condition
SETBP1 p.Arg498_Pro500del Likely pathogenic ★ same condition
SETBP1 p.Arg531fs Pathogenic ★ same condition
SETBP1 p.Gln211fs Pathogenic ★ same condition
SETBP1 p.Gly728fs 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-ser238fs (accessed [today's date]).

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