Is RAC2 p.Pro34Arg (c.101C>G) pathogenic?

RAC2 p.Pro34Arg (c.101C>G) is classified Uncertain significance in RAC2 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-09-08). AlphaMissense: likely pathogenic (0.9975); Absent from gnomAD v4.1; Associated with neutrophil immunodeficiency syndrome.

What condition is associated with RAC2 p.Pro34Arg (c.101C>G)?

RAC2 p.Pro34Arg (c.101C>G) is associated with neutrophil immunodeficiency syndrome (ClinVar).

How common is RAC2 p.Pro34Arg (c.101C>G) in the general population?

RAC2 p.Pro34Arg (c.101C>G) is absent from gnomAD v4.1 (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.

What do computational predictors say about RAC2 p.Pro34Arg (c.101C>G)?

AlphaMissense predicts likely pathogenic (score 0.9975) — an in-silico prediction, not a clinical call.

RAC2 p.Pro34Arg

c.101C>G · rs1927393826 · VCV2759148

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9975 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

neutrophil immunodeficiency syndrome

Computational evidence

Protein change
AlphaMissense	0.9975	likely pathogenic
REVEL	0.796	moderately pathogenic-leaning
SaProt	LLR -15.10	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 1.9, phastCons 1
Regional constraint	o/e 0.16	constrained · MANE · 11 kb · p 8e-12 · regional, not allelic
Overall
CADD	31.0	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — 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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: RAC2
Protein: p.Pro34Arg
Coding: c.101C>G
MANE Select: NM_002872
dbSNP: rs1927393826
Type: single nucleotide variant
Location: chr22:37241593 (GRCh38)
Gene constraint: LOEUF 0.197 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 93.56 · 4 PDB
Residue 34: a UniProt-annotated variant site (in imd73b; uncertain significance; increased interaction with pak1 compared to wild-type; potential gain-of-function variant)

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.Pro34His Likely pathogenic ★ same residue
RAC2 p.Pro34= Likely benign ★ 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

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-pro34arg (accessed [today's date]).

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