Is RAC1 p.Ser71Phe (c.212C>T) pathogenic?

RAC1 p.Ser71Phe (c.212C>T) is classified Pathogenic/Likely pathogenic in RAC1 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2023-02-21). AlphaMissense: likely pathogenic (0.9987); Absent from gnomAD v4.1; Associated with intellectual disability, autosomal dominant 48.

What condition is associated with RAC1 p.Ser71Phe (c.212C>T)?

RAC1 p.Ser71Phe (c.212C>T) is associated with intellectual disability, autosomal dominant 48 (ClinVar).

How common is RAC1 p.Ser71Phe (c.212C>T) in the general population?

RAC1 p.Ser71Phe (c.212C>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about RAC1 p.Ser71Phe (c.212C>T)?

AlphaMissense predicts likely pathogenic (score 0.9987) — an in-silico prediction, not a clinical call.

RAC1 p.Ser71Phe

c.212C>T · rs2115201430 · VCV1685419

Pathogenic/Likely pathogenic Multiple submitters

Classification

Pathogenic/Likely pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely pathogenic

0.9987 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

intellectual disability, autosomal dominant 48

Computational evidence

Protein change
AlphaMissense	0.9987	likely pathogenic ✓ concordant with ClinVar · top 1% in RAC1
REVEL	0.784	moderately pathogenic-leaning
SaProt	LLR -13.59	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 7.6	GERP 4.6, phastCons 1
Overall
CADD	29.9	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: RAC1
Protein: p.Ser71Phe
Coding: c.212C>T
MANE Select: NM_002933 · reported on NM_006908
dbSNP: rs2115201430
Type: single nucleotide variant
Location: chr7:6392028 (GRCh38)
Structure: AlphaFold pLDDT 92.87 · 12 PDB
Residue 71: a disulfide bond; a β-strand; a binding site

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.Arg66Ser Likely pathogenic ★★ same condition
RAC1 p.Asn39Ser Pathogenic/Likely pathogenic ★★ same condition
RAC1 p.Pro73Leu 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
RAC1 p.Leu165= Benign/Likely benign ★★ same condition
RAC1 p.Ala159Thr 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-ser71phe (accessed [today's date]).

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