Is SETBP1 p.Ser644= (c.1932C>T) pathogenic?

SETBP1 p.Ser644= (c.1932C>T) is classified Conflicting classifications of pathogenicity in SETBP1 (ClinVar, Conflicting submitters, 5 submitters; last evaluated 2026-01-21). Low-frequency (popmax 2.24%, eas); Associated with Schinzel-Giedion syndrome.

What condition is associated with SETBP1 p.Ser644= (c.1932C>T)?

SETBP1 p.Ser644= (c.1932C>T) is associated with Schinzel-Giedion syndrome (ClinVar).

How common is SETBP1 p.Ser644= (c.1932C>T) in the general population?

SETBP1 p.Ser644= (c.1932C>T) is low-frequency (popmax 2.24%, eas) (gnomAD).

SETBP1 p.Ser644=

c.1932C>T · rs3744824 · VCV159870

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 5 submitters

gnomAD v4.1

Rare

low-frequency (popmax 2.24%, eas)

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 -4.6	GERP -5.4
Overall
CADD	5.299	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 2.24% East Asian · 1,004/44,872 alleles

Filtering AF 2.12% ClinGen BA1/BS1 input FAF95, joint · FAF99 2.08%

Overall 0.0651% 1,050/1,613,612 alleles · low-frequency

Ancestry group	Frequency	1 in
East Asiangrpmax	2.24%	45
Remaining individualsnot grpmax-eligible	0.0464%	2,155
Middle Eastern	0.0165%	6,062
South Asian	0.00329%	30,358
African / African-American	0.00267%	37,495
European (non-Finnish)	0.000932%	107,274

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.Ser644=
Coding: c.1932C>T
MANE Select: NM_015559
dbSNP: rs3744824
Type: single nucleotide variant
Location: chr18:44951272 (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.Ser644Asn Uncertain significance ★ ⚠ same residue
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

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-ser644 (accessed [today's date]).

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