Is SATB2 p.Pro28fs (c.83del) pathogenic?

SATB2 p.Pro28fs (c.83del) is classified Pathogenic in SATB2 (ClinVar, Single submitter, 1 submitter; last evaluated 2016-04-08). Very rare (popmax 6.5e-05%).

How common is SATB2 p.Pro28fs (c.83del) in the general population?

SATB2 p.Pro28fs (c.83del) is very rare (popmax 6.5e-05%) (gnomAD).

SATB2 p.Pro28fs

c.83del · rs886041685 · VCV280492

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 6.5e-05%)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function in a haploinsufficient gene (ClinGen)
NMD	predicted	premature termination codon in exon 2 of 11
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP -0.13	GERP 0.65, phastCons 0.51

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 6.5e-05%

Overall 6.5e-05% 1/1,538,518 alleles · very rare exomes 1/1,386,248 · genomes 0/152,270 · joint denominator

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.Pro28fs
Coding: c.83del
MANE Select: NM_001172509
dbSNP: rs886041685
Type: Deletion
Location: chr2:199455955 (GRCh38)
Gene constraint: LOEUF 0.077 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 66.87 · 3 PDB
Residue 28: the 'disordered' region

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

Similar variants

SATB2 p.Gln270fs Pathogenic ★★ same type
SATB2 c.1174-16del Benign/Likely benign ★★ same type
SATB2 c.1740+20_1740+29del Likely benign ★★ same type
SATB2 c.598-4del Likely benign ★★ same type
SATB2 c.473+1del Likely pathogenic ★ same type
SATB2 c.474-2_474-1del Likely pathogenic ★ same type
SATB2 p.Ala383fs Pathogenic ★ same type
SATB2 p.Ala407fs 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-pro28fs (accessed [today's date]).

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