Is RAC2 p.Phe169= (c.507C>T) pathogenic?

RAC2 p.Phe169= (c.507C>T) is classified Likely benign in RAC2 (ClinVar, Multiple submitters, 5 submitters; last evaluated 2026-04-06). Ultra-rare (popmax 0.0451%, nfe); Associated with neutrophil immunodeficiency syndrome.

What condition is associated with RAC2 p.Phe169= (c.507C>T)?

RAC2 p.Phe169= (c.507C>T) is associated with neutrophil immunodeficiency syndrome (ClinVar).

How common is RAC2 p.Phe169= (c.507C>T) in the general population?

RAC2 p.Phe169= (c.507C>T) is ultra-rare (popmax 0.0451%, 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.Phe169=

c.507C>T · rs150782757 · VCV1088056

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 5 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0451%, nfe)

Conditions

neutrophil immunodeficiency syndrome

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP -6.7	GERP -3.8
Overall
CADD	0.171	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0451% European (non-Finnish) · 532/1,179,588 alleles

Filtering AF 0.0419% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0406%

Overall 0.0356% 574/1,612,980 alleles · ultra-rare exomes 535/1,461,022 · genomes 39/151,958 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.0451%	2,217
African / African-American	0.0174%	5,752
Remaining individualsnot grpmax-eligible	0.016%	6,244
Admixed American	0.0117%	8,562
Finnishnot grpmax-eligible	0.011%	9,105
East Asian	0.00891%	11,218
South Asian	0.0011%	91,064

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.Phe169=
Coding: c.507C>T
MANE Select: NM_002872
dbSNP: rs150782757
Type: single nucleotide variant
Location: chr22:37226745 (GRCh38)
Gene constraint: LOEUF 0.197 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 93.56 · 4 PDB
Residue 169: a UniProt-annotated variant site (in imd73c; strong decrease in protein expression); an α-helix

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.Phe169Leu 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-phe169 (accessed [today's date]).

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