Is SATB2 p.Pro135= (c.405C>T) pathogenic?

SATB2 p.Pro135= (c.405C>T) is classified Benign/Likely benign in SATB2 (ClinVar, Multiple submitters, 5 submitters; last evaluated 2026-07-01). Rare (popmax 0.418%, amr); Associated with chromosome 2q32-q33 deletion syndrome.

What condition is associated with SATB2 p.Pro135= (c.405C>T)?

SATB2 p.Pro135= (c.405C>T) is associated with chromosome 2q32-q33 deletion syndrome (ClinVar).

How common is SATB2 p.Pro135= (c.405C>T) in the general population?

SATB2 p.Pro135= (c.405C>T) is rare (popmax 0.418%, amr) (gnomAD).

SATB2 p.Pro135=

c.405C>T · rs150990155 · VCV469558

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 5 submitters

gnomAD v4.1

Rare

rare (popmax 0.418%, amr)

Conditions

chromosome 2q32-q33 deletion 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 -1.8	GERP -8.4
Overall
CADD	3.452	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.418% Admixed American · 251/60,006 alleles

Filtering AF 0.376% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.359%

Overall 0.0175% 282/1,613,978 alleles · rare exomes 261/1,461,780 · genomes 21/152,198 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.418%	239
Remaining individualsnot grpmax-eligible	0.0048%	20,833
East Asian	0.00446%	22,437
South Asian	0.0022%	45,537
European (non-Finnish)	0.00203%	49,164

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: SATB2
Protein: p.Pro135=
Coding: c.405C>T
MANE Select: NM_001172509
dbSNP: rs150990155
Type: single nucleotide variant
Location: chr2:199381762 (GRCh38)
Gene constraint: LOEUF 0.077 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 66.87 · 3 PDB
Residue 135: the cmp domain

Full SATB2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

chromosome 2q32-q33 deletion syndrome — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

SATB2 c.1174-2A>G Pathogenic ★★ same condition
SATB2 c.474-2A>G Pathogenic ★★ same condition
SATB2 c.597+1G>A Pathogenic/Likely pathogenic ★★ same condition
SATB2 c.700+1G>A Likely pathogenic ★★ same condition
SATB2 p.Arg239Ter Pathogenic ★★ same condition
SATB2 p.Arg283Ter Pathogenic ★★ same condition
SATB2 p.Arg389Cys Pathogenic/Likely pathogenic ★★ same condition
SATB2 p.Arg389Leu 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/satb2-p-pro135 (accessed [today's date]).

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