Is SATB2 p.Val55Ala (c.164T>C) pathogenic?

SATB2 p.Val55Ala (c.164T>C) is classified Benign in SATB2 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-03-03). AlphaMissense: likely benign (0.0652); Very rare (popmax 0.00218%, nfe); Associated with chromosome 2q32-q33 deletion syndrome.

What condition is associated with SATB2 p.Val55Ala (c.164T>C)?

SATB2 p.Val55Ala (c.164T>C) is associated with chromosome 2q32-q33 deletion syndrome (ClinVar).

How common is SATB2 p.Val55Ala (c.164T>C) in the general population?

SATB2 p.Val55Ala (c.164T>C) is very rare (popmax 0.00218%, nfe) (gnomAD).

What do computational predictors say about SATB2 p.Val55Ala (c.164T>C)?

AlphaMissense predicts likely benign (score 0.0652) — an in-silico prediction, not a clinical call.

SATB2 p.Val55Ala

c.164T>C · rs1226310700 · VCV2913773

Benign Single submitter

Classification

Benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0652 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00218%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

chromosome 2q32-q33 deletion syndrome

Computational evidence

Protein change
AlphaMissense	0.0652	likely benign
REVEL	0.134	moderately benign-leaning
SaProt	LLR -5.30	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 9	GERP 1.8, phastCons 1
Regional constraint	o/e 0.65	unconstrained · MANE · 23 kb · p 0.00022 · regional, not allelic
Overall
CADD	22.2	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 0.00218% European (non-Finnish) · 25/1,147,780 alleles

Filtering AF 0.0015% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00126%

Overall 0.00188% 26/1,384,544 alleles · very rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00218%	45,911
South Asian	0.00119%	84,044

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.Val55Ala
Coding: c.164T>C
MANE Select: NM_001172509
dbSNP: rs1226310700
Type: single nucleotide variant
Location: chr2:199455874 (GRCh38)
Gene constraint: LOEUF 0.077 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 66.87 · 3 PDB

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 p.Val55Met Uncertain significance ★★ ⚠ same residue
SATB2 p.Val55Leu Likely benign ★★ same residue
SATB2 p.Val55= Likely benign ★ 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
SATB2 c.700+1G>A Likely pathogenic ★★ same condition
SATB2 p.Arg239Ter 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-val55ala (accessed [today's date]).

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