Is SATB2 p.Val476= (c.1428G>A) pathogenic?

SATB2 p.Val476= (c.1428G>A) is classified Likely benign in SATB2 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-04-01). Very rare (popmax 0.00102%, nfe); Associated with chromosome 2q32-q33 deletion syndrome.

What condition is associated with SATB2 p.Val476= (c.1428G>A)?

SATB2 p.Val476= (c.1428G>A) is associated with chromosome 2q32-q33 deletion syndrome (ClinVar).

How common is SATB2 p.Val476= (c.1428G>A) in the general population?

SATB2 p.Val476= (c.1428G>A) is very rare (popmax 0.00102%, nfe) (gnomAD).

SATB2 p.Val476=

c.1428G>A · rs753471227 · VCV537282

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00102%, nfe)

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 6	GERP 2.5, phastCons 1
Overall
CADD	12.6	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00102% European (non-Finnish) · 12/1,179,568 alleles

Filtering AF 0.000542% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000429%

Overall 0.00089% 13/1,461,324 alleles · very rare

Ancestry group	Frequency	1 in
Remaining individualsnot grpmax-eligible	0.0016%	62,472
European (non-Finnish)grpmax	0.00102%	98,297

Remaining individuals shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Val476=
Coding: c.1428G>A
MANE Select: NM_001172509
dbSNP: rs753471227
Type: single nucleotide variant
Location: chr2:199323917 (GRCh38)
Gene constraint: LOEUF 0.077 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 66.87 · 3 PDB
Residue 476: 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.Val476Leu Uncertain significance ★ ⚠ same residue
SATB2 p.Val476Ala 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

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-val476 (accessed [today's date]).

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