Is RASGRP2 p.Arg494fs (c.1480dup) pathogenic?

RASGRP2 p.Arg494fs (c.1480dup) is classified Likely pathogenic in RASGRP2 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2016-08-06). No gnomAD frequency available for this variant; Associated with platelet-type bleeding disorder 18.

What condition is associated with RASGRP2 p.Arg494fs (c.1480dup)?

RASGRP2 p.Arg494fs (c.1480dup) is associated with platelet-type bleeding disorder 18 (ClinVar).

How common is RASGRP2 p.Arg494fs (c.1480dup) in the general population?

RASGRP2 p.Arg494fs (c.1480dup) is no gnomAD frequency available for this variant (gnomAD).

How is Bleeding disorder due to CalDAG-GEFI deficiency inherited?

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

RASGRP2 p.Arg494fs

c.1480dup · rs1555122100 · VCV417937

Likely pathogenic No assertion criteria

Classification

Likely pathogenic

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Not reported

no gnomAD frequency available for this variant

Conditions

platelet-type bleeding disorder 18

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function
NMD	predicted	premature termination codon in exon 13 of 17
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 3.2	GERP 0.78, phastCons 1

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

dbSNP / gnomAD

No gnomAD frequency available for this variant. This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: RASGRP2
Protein: p.Arg494fs
Coding: c.1480dup
MANE Select: NM_001098671
dbSNP: rs1555122100
Type: Duplication
Location: chr11:64730126 (GRCh38)
Gene constraint: LOEUF 0.854 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 77.48 · 2 PDB
Residue 494: a UniProt-annotated variant site (in bdplt18); a UniProt-annotated variant site (in bdplt18; lack of mutant protein in platelets from a patient homozygous for the mutation)

Full RASGRP2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

platelet-type bleeding disorder 18 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Bleeding disorder due to CalDAG-GEFI deficiency (Orphanet):

Inheritance: Autosomal recessive
Onset: Infancy

Similar variants

RASGRP2 p.Arg494Cys Uncertain significance ★ ⚠ same residue
RASGRP2 p.Gly305Asp Likely pathogenic ★★ same condition
RASGRP2 p.Phe497fs Pathogenic/Likely pathogenic ★★ same condition
RASGRP2 c.1096-44T>C Benign ★★ same condition
RASGRP2 c.1174-43T>C Benign ★★ same condition
RASGRP2 c.1591+45T>G Benign ★★ same condition
RASGRP2 c.372-45T>G Benign ★★ same condition
RASGRP2 c.523-34A>G 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/rasgrp2-p-arg494fs (accessed [today's date]).

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