Is SATB2 p.Asp477= (c.1431C>T) pathogenic?

SATB2 p.Asp477= (c.1431C>T) is classified Likely benign in SATB2 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-03-31). Ultra-rare (popmax 0.033%, mid); Associated with chromosome 2q32-q33 deletion syndrome.

What condition is associated with SATB2 p.Asp477= (c.1431C>T)?

SATB2 p.Asp477= (c.1431C>T) is associated with chromosome 2q32-q33 deletion syndrome (ClinVar).

How common is SATB2 p.Asp477= (c.1431C>T) in the general population?

SATB2 p.Asp477= (c.1431C>T) is ultra-rare (popmax 0.033%, mid) (gnomAD).

SATB2 p.Asp477=

c.1431C>T · rs765952558 · VCV1127258

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.033%, mid)

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 -1.1	GERP -0.96
Overall
CADD	9.64	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.033% Middle Eastern · 2/6,054 alleles

Filtering AF 0.00583% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00242%

Overall 0.00246% 36/1,461,302 alleles · ultra-rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.033%	3,027
European (non-Finnish)	0.00254%	39,318
South Asian	0.0022%	45,524
Admixed American	0.00167%	59,954
Remaining individualsnot grpmax-eligible	0.0016%	62,472

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.Asp477=
Coding: c.1431C>T
MANE Select: NM_001172509
dbSNP: rs765952558
Type: single nucleotide variant
Location: chr2:199323914 (GRCh38)
Gene constraint: LOEUF 0.077 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 66.87 · 3 PDB
Residue 477: 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 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-asp477 (accessed [today's date]).

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