Is SATB2 p.Arg399Pro (c.1196G>C) pathogenic?

SATB2 p.Arg399Pro (c.1196G>C) is classified Conflicting classifications of pathogenicity in SATB2 (ClinVar, Conflicting submitters, 3 submitters; last evaluated 2024-11-07). AlphaMissense: likely pathogenic (0.9999); Absent from gnomAD v4.1; Associated with Inborn genetic diseases.

What condition is associated with SATB2 p.Arg399Pro (c.1196G>C)?

SATB2 p.Arg399Pro (c.1196G>C) is associated with Inborn genetic diseases, chromosome 2q32-q33 deletion syndrome (ClinVar).

How common is SATB2 p.Arg399Pro (c.1196G>C) in the general population?

SATB2 p.Arg399Pro (c.1196G>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about SATB2 p.Arg399Pro (c.1196G>C)?

AlphaMissense predicts likely pathogenic (score 0.9999) — an in-silico prediction, not a clinical call.

SATB2 p.Arg399Pro

c.1196G>C · rs1057518190 · VCV588166

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 3 submitters

AlphaMissense

likely pathogenic

0.9999 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.9999	likely pathogenic · top 6% in SATB2
REVEL	0.626	indeterminate
SaProt	LLR -15.30	damaging
⇒ AlphaMissense and SaProt both call this damaging; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.7	GERP 2.5, phastCons 1
Regional constraint	o/e 0.23	constrained · MANE · 20 kb · p 9.2e-14 · regional, not allelic
Overall
CADD	33.0	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.Arg399Pro
Coding: c.1196G>C
MANE Select: NM_001172509
dbSNP: rs1057518190
Type: single nucleotide variant
Location: chr2:199328888 (GRCh38)
Gene constraint: LOEUF 0.077 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 66.87 · 3 PDB
Residue 399: a DNA-binding region; an α-helix

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

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: chromosome 2q32-q33 deletion syndrome

Similar variants

SATB2 p.Arg399Cys Pathogenic/Likely pathogenic ★★ same residue
SATB2 p.Arg399His Pathogenic/Likely pathogenic ★★ ⚠ same residue
SATB2 p.Arg399fs Pathogenic ★ same residue
SATB2 p.Arg399Leu Pathogenic/Likely pathogenic ★★ same residue
SATB2 p.Arg399Gly Pathogenic ★ 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

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-arg399pro (accessed [today's date]).

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