Is SATB2 p.Pro468= (c.1404G>A) pathogenic?

SATB2 p.Pro468= (c.1404G>A) is classified Likely benign in SATB2 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-06-29). Ultra-rare (popmax 0.0165%, mid); Associated with chromosome 2q32-q33 deletion syndrome.

What condition is associated with SATB2 p.Pro468= (c.1404G>A)?

SATB2 p.Pro468= (c.1404G>A) is associated with chromosome 2q32-q33 deletion syndrome (ClinVar).

How common is SATB2 p.Pro468= (c.1404G>A) in the general population?

SATB2 p.Pro468= (c.1404G>A) is ultra-rare (popmax 0.0165%, mid) (gnomAD).

SATB2 p.Pro468=

c.1404G>A · rs542911998 · VCV1593078

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.0165%, 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 3.3	GERP 2.5, phastCons 1
Overall
CADD	14.62	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0165% Middle Eastern · 1/6,052 alleles

Filtering AF 0.00211% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00137%

Overall 0.00205% 33/1,613,200 alleles · ultra-rare exomes 29/1,461,240 · genomes 4/151,960 · joint denominator

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0165%	6,052
South Asian	0.00549%	18,202
African / African-American	0.004%	24,972
Remaining individualsnot grpmax-eligible	0.0032%	31,233
East Asian	0.00223%	44,866
European (non-Finnish)	0.00178%	56,166

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.Pro468=
Coding: c.1404G>A
MANE Select: NM_001172509
dbSNP: rs542911998
Type: single nucleotide variant
Location: chr2:199323941 (GRCh38)
Gene constraint: LOEUF 0.077 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 66.87 · 3 PDB
Residue 468: the 'disordered' 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.Pro468Leu Benign ★ same residue
SATB2 p.Pro468Thr 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

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-pro468 (accessed [today's date]).

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