Is RASGRP1 p.Arg341= (c.1023G>A) pathogenic?

RASGRP1 p.Arg341= (c.1023G>A) is classified Uncertain significance in RASGRP1 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-03-02). Absent from gnomAD v4.1; Associated with immunodeficiency 64.

What condition is associated with RASGRP1 p.Arg341= (c.1023G>A)?

RASGRP1 p.Arg341= (c.1023G>A) is associated with immunodeficiency 64 (ClinVar).

How common is RASGRP1 p.Arg341= (c.1023G>A) in the general population?

RASGRP1 p.Arg341= (c.1023G>A) is absent from gnomAD v4.1 (gnomAD).

RASGRP1 p.Arg341=

Q: How is EBV-induced lymphoproliferative disease due to RASGRP1 deficiency inherited?

Typically Autosomal recessive (Orphanet). A genetic counselor can assess individual risk for a family.

c.1023G>A · rs2141104454 · VCV1675118

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Absent

absent from gnomAD v4.1

Conditions

immunodeficiency 64

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 0.12	GERP 0.45, phastCons 0.93
Overall
CADD	8.512	PHRED · no single calibrated threshold — expert panels disagree

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: RASGRP1
Protein: p.Arg341=
Coding: c.1023G>A
MANE Select: NM_005739
dbSNP: rs2141104454
Type: single nucleotide variant
Location: chr15:38507945 (GRCh38)
Gene constraint: LOEUF 0.538 · pLI 0.48 (gnomAD)
Structure: AlphaFold pLDDT 72.43 · 2 PDB
Residue 341: the ras-gef domain; a UniProt-annotated variant site (in imd64; loss of protein expression); a UniProt-annotated variant site (in imd64); a UniProt-annotated variant site (in imd64; no effect on protein expression; decreased t cell activation); an α-helix

Full RASGRP1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

immunodeficiency 64 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For EBV-induced lymphoproliferative disease due to RASGRP1 deficiency (Orphanet):

Inheritance: Autosomal recessive

Similar variants

RASGRP1 p.Arg341Trp Uncertain significance ★ ⚠ same residue
RASGRP1 c.327-1C>G Pathogenic/Likely pathogenic ★★ same condition
RASGRP1 p.Arg81Ter Pathogenic/Likely pathogenic ★★ same condition
RASGRP1 p.Tyr387His Uncertain significance ★★ ⚠ same condition
RASGRP1 c.676-16G>T Benign/Likely benign ★★ same condition
RASGRP1 p.Asn292= Benign/Likely benign ★★ same condition
RASGRP1 p.Asp143= Benign/Likely benign ★★ same condition
RASGRP1 p.Phe495= Benign ★★ 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/rasgrp1-p-arg341 (accessed [today's date]).

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