Is RAC2 p.Ser190= (c.570C>T) pathogenic?

RAC2 p.Ser190= (c.570C>T) is classified Likely benign in RAC2 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-09-30). Very rare (popmax 0.000509%, nfe); Associated with neutrophil immunodeficiency syndrome.

What condition is associated with RAC2 p.Ser190= (c.570C>T)?

RAC2 p.Ser190= (c.570C>T) is associated with neutrophil immunodeficiency syndrome (ClinVar).

How common is RAC2 p.Ser190= (c.570C>T) in the general population?

RAC2 p.Ser190= (c.570C>T) is very rare (popmax 0.000509%, nfe) (gnomAD).

How is Infantile LAD-like disease due to RAC2 deficiency inherited?

Typically Autosomal dominant (Orphanet). A genetic counselor can assess individual risk for a family.

RAC2 p.Ser190=

c.570C>T · VCV4808694

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.000509%, nfe)

Conditions

neutrophil immunodeficiency syndrome

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 3.9	GERP -2.6, phastCons 1
Overall
CADD	9.558	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.000509% European (non-Finnish) · 6/1,179,440 alleles

Filtering AF 0.000183% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00012%

Overall 0.000372% 6/1,612,730 alleles · very rare exomes 5/1,460,674 · genomes 1/152,056 · 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: RAC2
Protein: p.Ser190=
Coding: c.570C>T
MANE Select: NM_002872
Type: single nucleotide variant
Location: chr22:37226682 (GRCh38)
Gene constraint: LOEUF 0.197 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 93.56 · 4 PDB
Residue 190: a UniProt-annotated variant site (in imd73c; strong decrease in protein expression)

Full RAC2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

neutrophil immunodeficiency syndrome — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Infantile LAD-like disease due to RAC2 deficiency (Orphanet):

Inheritance: Autosomal dominant
Onset: Infancy, Neonatal

Similar variants

RAC2 p.Ser190Thr Uncertain significance ★ ⚠ same residue
RAC2 p.Glu62Lys Pathogenic/Likely pathogenic ★★ same condition
RAC2 p.Ala95Thr Uncertain significance ★★ ⚠ same condition
RAC2 p.Arg174Trp Uncertain significance ★★ ⚠ same condition
RAC2 p.Arg183Trp Uncertain significance ★★ ⚠ same condition
RAC2 p.Arg66His Uncertain significance ★★ ⚠ same condition
RAC2 p.Arg68Trp Uncertain significance ★★ ⚠ same condition
RAC2 p.Asp63Asn 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/rac2-p-ser190 (accessed [today's date]).

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