Is SETBP1 p.Ser1192= (c.3576C>T) pathogenic?

SETBP1 p.Ser1192= (c.3576C>T) is classified Benign/Likely benign in SETBP1 (ClinVar, Multiple submitters, 5 submitters; last evaluated 2026-01-01). Rare (popmax 0.148%, mid); Associated with Schinzel-Giedion syndrome.

What condition is associated with SETBP1 p.Ser1192= (c.3576C>T)?

SETBP1 p.Ser1192= (c.3576C>T) is associated with Schinzel-Giedion syndrome (ClinVar).

How common is SETBP1 p.Ser1192= (c.3576C>T) in the general population?

SETBP1 p.Ser1192= (c.3576C>T) is rare (popmax 0.148%, mid) (gnomAD).

SETBP1 p.Ser1192=

c.3576C>T · rs201826395 · VCV326752

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 5 submitters

gnomAD v4.1

Rare

rare (popmax 0.148%, mid)

Conditions

Schinzel-Giedion syndrome

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -10	GERP -5.7
Overall
CADD	1.965	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.148% Middle Eastern · 9/6,062 alleles

Filtering AF 0.0774% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0578%

Overall 0.0167% 269/1,614,156 alleles · rare exomes 227/1,461,886 · genomes 42/152,270 · joint denominator

Ancestry group	Frequency	1 in
Finnishnot grpmax-eligible	0.2%	500
Middle Easterngrpmax	0.148%	674
East Asian	0.0646%	1,548
South Asian	0.0538%	1,859
Remaining individualsnot grpmax-eligible	0.0368%	2,718
Admixed American	0.00666%	15,006
African / African-American	0.004%	25,011
European (non-Finnish)	0.00203%	49,168

Finnish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

Rarity supports pathogenicity (ACMG PM2); frequency above a disease-specific BA1/BS1 threshold argues against it. A variant frequent in one ancestry group can be near-absent in others, so a single global figure can mislead.

Variant & gene context

Gene: SETBP1
Protein: p.Ser1192=
Coding: c.3576C>T
MANE Select: NM_015559
dbSNP: rs201826395
Type: single nucleotide variant
Location: chr18:44952916 (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

Disease context

Schinzel-Giedion syndrome — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

SETBP1 p.Arg589Ter Pathogenic ★★ same condition
SETBP1 p.Arg625Ter Pathogenic ★★ same condition
SETBP1 p.Arg626Ter Pathogenic ★★ same condition
SETBP1 p.Asp868Asn Pathogenic ★★ ⚠ same condition
SETBP1 p.Asp868His Pathogenic/Likely pathogenic ★★ ⚠ same condition
SETBP1 p.Glu858Lys Pathogenic/Likely pathogenic ★★ ⚠ same condition
SETBP1 p.Gly870Asp Pathogenic/Likely pathogenic ★★ ⚠ same condition
SETBP1 p.Gly870Ser 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-ser1192 (accessed [today's date]).

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