Is SATB2 p.Ala407= (c.1221C>T) pathogenic?

SATB2 p.Ala407= (c.1221C>T) is classified Likely benign in SATB2 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-06-16). Ultra-rare (popmax 0.0245%, eas); Associated with chromosome 2q32-q33 deletion syndrome.

What condition is associated with SATB2 p.Ala407= (c.1221C>T)?

SATB2 p.Ala407= (c.1221C>T) is associated with chromosome 2q32-q33 deletion syndrome (ClinVar).

How common is SATB2 p.Ala407= (c.1221C>T) in the general population?

SATB2 p.Ala407= (c.1221C>T) is ultra-rare (popmax 0.0245%, eas) (gnomAD).

SATB2 p.Ala407=

c.1221C>T · rs750531398 · VCV2195158

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.0245%, eas)

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	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 0.095	GERP -2.1, phastCons 0.73
Overall
CADD	12.22	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0245% East Asian · 11/44,856 alleles

Filtering AF 0.0137% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0106%

Overall 0.000805% 13/1,613,936 alleles · ultra-rare exomes 13/1,461,678 · genomes 0/152,258 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.0245%	4,078
European (non-Finnish)	0.00017%	589,960

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.Ala407=
Coding: c.1221C>T
MANE Select: NM_001172509
dbSNP: rs750531398
Type: single nucleotide variant
Location: chr2:199328863 (GRCh38)
Gene constraint: LOEUF 0.077 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 66.87 · 3 PDB
Residue 407: 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.Ala407fs Likely pathogenic ★ 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-ala407 (accessed [today's date]).

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