Is RAC3 p.Ser41Phe (c.122C>T) pathogenic?

RAC3 p.Ser41Phe (c.122C>T) is classified Uncertain significance in RAC3 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-06-03). AlphaMissense: likely pathogenic (0.9626); Absent from gnomAD v4.1.

How common is RAC3 p.Ser41Phe (c.122C>T) in the general population?

RAC3 p.Ser41Phe (c.122C>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about RAC3 p.Ser41Phe (c.122C>T)?

AlphaMissense predicts likely pathogenic (score 0.9626) — an in-silico prediction, not a clinical call.

RAC3 p.Ser41Phe

c.122C>T · VCV4536597

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9626 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.9626	likely pathogenic
REVEL	0.644	pathogenic-leaning
SaProt	LLR -16.37	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 5.8	GERP 0.8, phastCons 1
Regional constraint	o/e 0.73	unconstrained · MANE · 1,001 bp · p 0.025 · regional, not allelic
Overall
CADD	28.2	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: RAC3
Protein: p.Ser41Phe
Coding: c.122C>T
MANE Select: NM_005052
Type: single nucleotide variant
Location: chr17:82032725 (GRCh38)
Gene constraint: LOEUF 0.726 · pLI 0.28 (gnomAD)
Structure: AlphaFold pLDDT 93.92 · 6 PDB
Residue 41: a β-strand

Full RAC3 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

RAC3 p.Asp63Asn Pathogenic/Likely pathogenic ★★ same type
RAC3 p.Glu62Lys Pathogenic ★★ same type
RAC3 p.Lys116Asn Pathogenic/Likely pathogenic ★★ same type
RAC3 p.Tyr64Cys Likely pathogenic ★★ same type
RAC3 p.Arg120Cys Uncertain significance ★★ ⚠ same type
RAC3 p.Arg130Gln Uncertain significance ★★ ⚠ same type
RAC3 p.Arg174Cys Uncertain significance ★★ ⚠ same type
RAC3 p.Asn92Lys Likely pathogenic ★ same type

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/rac3-p-ser41phe (accessed [today's date]).

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