Is SATB2 p.Ser357Pro (c.1069T>C) pathogenic?

SATB2 p.Ser357Pro (c.1069T>C) is classified Uncertain significance in SATB2 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-11-12). AlphaMissense: likely benign (0.1159); Absent from gnomAD v4.1; Associated with chromosome 2q32-q33 deletion syndrome.

What condition is associated with SATB2 p.Ser357Pro (c.1069T>C)?

SATB2 p.Ser357Pro (c.1069T>C) is associated with chromosome 2q32-q33 deletion syndrome (ClinVar).

How common is SATB2 p.Ser357Pro (c.1069T>C) in the general population?

SATB2 p.Ser357Pro (c.1069T>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about SATB2 p.Ser357Pro (c.1069T>C)?

AlphaMissense predicts likely benign (score 0.1159) — an in-silico prediction, not a clinical call.

SATB2 p.Ser357Pro

c.1069T>C · VCV3665921

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1159 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

chromosome 2q32-q33 deletion syndrome

Computational evidence

Protein change
AlphaMissense	0.1159	likely benign
REVEL	0.178	moderately benign-leaning
SaProt	LLR -6.27	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 11	GERP 2.2, phastCons 1
Regional constraint	o/e 0.63	unconstrained · MANE · 131 bp · p 0.0064 · regional, not allelic
Overall
CADD	22.5	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: SATB2
Protein: p.Ser357Pro
Coding: c.1069T>C
MANE Select: NM_001172509
Type: single nucleotide variant
Location: chr2:199348805 (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

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

Similar variants

SATB2 p.Ser357= Benign/Likely benign ★★ 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-ser357pro (accessed [today's date]).

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