Is RAC1 p.Leu165= (c.495C>G) pathogenic?

RAC1 p.Leu165= (c.495C>G) is classified Benign/Likely benign in RAC1 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2025-10-01). Rare (popmax 0.337%, nfe); Associated with intellectual disability, autosomal dominant 48.

What condition is associated with RAC1 p.Leu165= (c.495C>G)?

RAC1 p.Leu165= (c.495C>G) is associated with intellectual disability, autosomal dominant 48 (ClinVar).

How common is RAC1 p.Leu165= (c.495C>G) in the general population?

RAC1 p.Leu165= (c.495C>G) is rare (popmax 0.337%, nfe) (gnomAD).

RAC1 p.Leu165=

c.495C>G · rs61753123 · VCV726231

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

gnomAD v4.1

Rare

rare (popmax 0.337%, nfe)

Conditions

intellectual disability, autosomal dominant 48

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 4	GERP 3.6, phastCons 1
Overall
CADD	11.98	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.337% European (non-Finnish) · 3,980/1,179,668 alleles

Filtering AF 0.329% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.325%

Overall 0.27% 4,361/1,612,264 alleles · rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.337%	296
Ashkenazi Jewishnot grpmax-eligible	0.257%	389
Remaining individualsnot grpmax-eligible	0.204%	491
Admixed American	0.181%	553
Middle Eastern	0.131%	763
African / African-American	0.0801%	1,248
Finnishnot grpmax-eligible	0.00469%	21,324

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: RAC1
Protein: p.Leu165=
Coding: c.495C>G
MANE Select: NM_002933 · reported on NM_006908
dbSNP: rs61753123
Type: single nucleotide variant
Location: chr7:6402362 (GRCh38)
Structure: AlphaFold pLDDT 92.87 · 12 PDB

Full RAC1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

intellectual disability, autosomal dominant 48 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

RAC1 p.Leu165Val Likely pathogenic ★ same residue
RAC1 p.Arg66Ser Likely pathogenic ★★ same condition
RAC1 p.Asn39Ser Pathogenic/Likely pathogenic ★★ same condition
RAC1 p.Pro73Leu Pathogenic/Likely pathogenic ★★ same condition
RAC1 p.Ser71Phe Pathogenic/Likely pathogenic ★★ same condition
RAC1 p.Tyr32His Pathogenic/Likely pathogenic ★★ same condition
RAC1 p.Tyr64Asp Pathogenic/Likely pathogenic ★★ same condition
RAC1 p.Val51Met Pathogenic/Likely 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/rac1-p-leu165 (accessed [today's date]).

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