Is SATB1 p.Pro282Ser (c.844C>T) pathogenic?

SATB1 p.Pro282Ser (c.844C>T) is classified Uncertain significance in SATB1 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-10-29). AlphaMissense: likely benign (0.0716); Very rare (popmax 0.00223%, eas); Associated with Inborn genetic diseases.

What condition is associated with SATB1 p.Pro282Ser (c.844C>T)?

SATB1 p.Pro282Ser (c.844C>T) is associated with Inborn genetic diseases (ClinVar).

How common is SATB1 p.Pro282Ser (c.844C>T) in the general population?

SATB1 p.Pro282Ser (c.844C>T) is very rare (popmax 0.00223%, eas) (gnomAD).

What do computational predictors say about SATB1 p.Pro282Ser (c.844C>T)?

AlphaMissense predicts likely benign (score 0.0716) — an in-silico prediction, not a clinical call.

SATB1 p.Pro282Ser

c.844C>T · VCV4630211

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0716 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00223%, eas)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.0716	likely benign
REVEL	0.449	indeterminate
SaProt	LLR -5.35	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 0.82, phastCons 1
Regional constraint	o/e 0.70	unconstrained · MANE · 2,683 bp · p 6.8e-05 · regional, not allelic
Overall
CADD	21.7	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00223% East Asian · 1/44,890 alleles

Overall 0.000186% 3/1,614,004 alleles · very rare exomes 2/1,461,826 · genomes 1/152,178 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00223%	44,890
Remaining individualsnot grpmax-eligible	0.0016%	62,486
European (non-Finnish)	8.47e-05%	1,180,025

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: SATB1
Protein: p.Pro282Ser
Coding: c.844C>T
MANE Select: NM_002971
Type: single nucleotide variant
Location: chr3:18394824 (GRCh38)
Gene constraint: LOEUF 0.209 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 65.88 · 8 PDB
Residue 282: the 'disordered' region

Full SATB1 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

Similar variants

SATB1 p.Arg627Gln Uncertain significance ★★ ⚠ same condition
SATB1 p.Pro181Ala Uncertain significance ★★ ⚠ same condition
SATB1 p.Thr367Asn Uncertain significance ★★ ⚠ same condition
SATB1 p.Val371Leu Uncertain significance ★★ ⚠ same condition
SATB1 c.211+2T>C Likely pathogenic ★ same condition
SATB1 p.Gln420Arg Likely pathogenic ★ ⚠ same condition
SATB1 c.1779+602C>T Uncertain significance ★ same condition
SATB1 c.1779+615A>G Uncertain significance ★ 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/satb1-p-pro282ser (accessed [today's date]).

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