Is SATB2 p.Ser263Pro (c.787T>C) pathogenic?

SATB2 p.Ser263Pro (c.787T>C) is classified Conflicting classifications of pathogenicity in SATB2 (ClinVar, Conflicting submitters, 5 submitters; last evaluated 2025-12-22). AlphaMissense: likely benign (0.0762); Rare (popmax 0.245%, eas); Associated with chromosome 2q32-q33 deletion syndrome.

What condition is associated with SATB2 p.Ser263Pro (c.787T>C)?

SATB2 p.Ser263Pro (c.787T>C) is associated with chromosome 2q32-q33 deletion syndrome (ClinVar).

How common is SATB2 p.Ser263Pro (c.787T>C) in the general population?

SATB2 p.Ser263Pro (c.787T>C) is rare (popmax 0.245%, eas) (gnomAD).

What do computational predictors say about SATB2 p.Ser263Pro (c.787T>C)?

AlphaMissense predicts likely benign (score 0.0762) — an in-silico prediction, not a clinical call.

SATB2 p.Ser263Pro

c.787T>C · rs12619995 · VCV1205443

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 5 submitters

AlphaMissense

likely benign

0.0762 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.245%, eas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

chromosome 2q32-q33 deletion syndrome

Computational evidence

Protein change
AlphaMissense	0.0762	likely benign
REVEL	0.08	moderately benign-leaning
SaProt	LLR -6.87	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 6.8	GERP 0.94, phastCons 1
Regional constraint	o/e 0.85	unconstrained · MANE · 20 kb · p 0.16 · regional, not allelic
Overall
CADD	21.2	PHRED · no single calibrated threshold — expert panels disagree

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.245% East Asian · 110/44,866 alleles

Filtering AF 0.208% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.194%

Overall 0.00719% 116/1,614,086 alleles · rare exomes 98/1,461,804 · genomes 18/152,282 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.245%	408
Remaining individualsnot grpmax-eligible	0.008%	12,501
South Asian	0.0011%	91,074

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.Ser263Pro
Coding: c.787T>C
MANE Select: NM_001172509
dbSNP: rs12619995
Type: single nucleotide variant
Location: chr2:199349087 (GRCh38)
Gene constraint: LOEUF 0.077 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 66.87 · 3 PDB
Residue 263: a UniProt-annotated variant site (in)

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-ser263pro (accessed [today's date]).

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