Is SATB2 p.Asn537Asp (c.1609A>G) pathogenic?

SATB2 p.Asn537Asp (c.1609A>G) is classified Uncertain significance in SATB2 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-06-11). AlphaMissense: likely pathogenic (0.9994); Absent from gnomAD v4.1.

How common is SATB2 p.Asn537Asp (c.1609A>G) in the general population?

SATB2 p.Asn537Asp (c.1609A>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about SATB2 p.Asn537Asp (c.1609A>G)?

AlphaMissense predicts likely pathogenic (score 0.9994) — an in-silico prediction, not a clinical call.

SATB2 p.Asn537Asp

c.1609A>G · rs2468839209 · VCV2507242

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9994 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Computational evidence

Protein change
AlphaMissense	0.9994	likely pathogenic · top 6% in SATB2
REVEL	0.316	indeterminate
SaProt	LLR -6.00	tolerated
⇒ AlphaMissense calls this damaging; SaProt does not; REVEL is indeterminate.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.9	GERP 2.5, phastCons 1
Regional constraint	o/e 0.54	unconstrained · MANE · 36 kb · p 1e-07 · regional, not allelic
Overall
CADD	32.0	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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: SATB2
Protein: p.Asn537Asp
Coding: c.1609A>G
MANE Select: NM_001172509
dbSNP: rs2468839209
Type: single nucleotide variant
Location: chr2:199308891 (GRCh38)
Gene constraint: LOEUF 0.077 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 66.87 · 3 PDB
Residue 537: a DNA-binding region; an α-helix

Full SATB2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

SATB2 p.Asn537fs Pathogenic ★ same residue
SATB2 c.1174-2A>G Pathogenic ★★ same type
SATB2 c.474-2A>G Pathogenic ★★ same type
SATB2 c.597+1G>A Pathogenic/Likely pathogenic ★★ same type
SATB2 c.700+1G>A Likely pathogenic ★★ same type
SATB2 p.Arg239Ter Pathogenic ★★ same type
SATB2 p.Arg283Ter Pathogenic ★★ same type
SATB2 p.Arg389Cys Pathogenic/Likely pathogenic ★★ same type

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-asn537asp (accessed [today's date]).

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