Is RAC2 p.Pro106Arg (c.317C>G) pathogenic?

RAC2 p.Pro106Arg (c.317C>G) is classified Uncertain significance in RAC2 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-07-03). AlphaMissense: ambiguous (0.4182); Absent from gnomAD v4.1; Associated with neutrophil immunodeficiency syndrome.

What condition is associated with RAC2 p.Pro106Arg (c.317C>G)?

RAC2 p.Pro106Arg (c.317C>G) is associated with neutrophil immunodeficiency syndrome (ClinVar).

How common is RAC2 p.Pro106Arg (c.317C>G) in the general population?

RAC2 p.Pro106Arg (c.317C>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.Pro106Arg (c.317C>G)?

AlphaMissense predicts ambiguous (score 0.4182) — an in-silico prediction, not a clinical call.

RAC2 p.Pro106Arg

c.317C>G · rs140997946 · VCV2005092

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.4182 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

2/2 damaging

REVEL, SaProt · AlphaMissense no call

Conditions

neutrophil immunodeficiency syndrome

Computational evidence

Protein change
AlphaMissense	0.4182	ambiguous
REVEL	0.65	pathogenic-leaning
SaProt	LLR -11.78	damaging
⇒ REVEL and SaProt both call this damaging; AlphaMissense makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 10	GERP 1.9, phastCons 1
Regional constraint	o/e 0.62	unconstrained · MANE · 6,193 bp · p 1.3e-07 · regional, not allelic
Overall
CADD	29.2	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

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.Pro106Arg
Coding: c.317C>G
MANE Select: NM_002872
dbSNP: rs140997946
Type: single nucleotide variant
Location: chr22:37231362 (GRCh38)
Gene constraint: LOEUF 0.197 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 93.56 · 4 PDB
Residue 106: a UniProt-annotated variant site (in imd73c; strong decrease in protein expression); a β-strand

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.Pro106Ala 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-pro106arg (accessed [today's date]).

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