Is SATB2 p.Ser357= (c.1071C>T) pathogenic?

SATB2 p.Ser357= (c.1071C>T) is classified Benign/Likely benign in SATB2 (ClinVar, Multiple submitters, 4 submitters; last evaluated 2026-01-26). Rare (popmax 0.107%, afr); Associated with Inborn genetic diseases.

What condition is associated with SATB2 p.Ser357= (c.1071C>T)?

SATB2 p.Ser357= (c.1071C>T) is associated with Inborn genetic diseases, chromosome 2q32-q33 deletion syndrome (ClinVar).

How common is SATB2 p.Ser357= (c.1071C>T) in the general population?

SATB2 p.Ser357= (c.1071C>T) is rare (popmax 0.107%, afr) (gnomAD).

SATB2 p.Ser357=

c.1071C>T · rs148055910 · VCV537279

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

gnomAD v4.1

Rare

rare (popmax 0.107%, afr)

Conditions

Inborn genetic diseases

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP -0.25	GERP -4.4, phastCons 0.002
Overall
CADD	8.79	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.107% African / African-American · 80/75,018 alleles

Filtering AF 0.0877% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0808%

Overall 0.00905% 146/1,612,388 alleles · rare exomes 95/1,460,106 · genomes 51/152,282 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.107%	938
East Asian	0.0201%	4,984
Middle Eastern	0.0165%	6,054
South Asian	0.0121%	8,273
Remaining individualsnot grpmax-eligible	0.00801%	12,491
Admixed American	0.00667%	14,997
European (non-Finnish)	0.00297%	33,673
Finnishnot grpmax-eligible	0.00156%	64,000

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.Ser357=
Coding: c.1071C>T
MANE Select: NM_001172509
dbSNP: rs148055910
Type: single nucleotide variant
Location: chr2:199348803 (GRCh38)
Gene constraint: LOEUF 0.077 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 66.87 · 3 PDB
Residue 357: a DNA-binding region

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

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: chromosome 2q32-q33 deletion syndrome

Similar variants

SATB2 p.Ser357Pro Uncertain significance ★ ⚠ same residue
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

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-ser357 (accessed [today's date]).

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