Is RASGRP2 p.Ile427= (c.1281C>T) pathogenic?

RASGRP2 p.Ile427= (c.1281C>T) is classified Likely benign in RASGRP2 (ClinVar, Single submitter, 1 submitter; last evaluated 2026-01-03). Very rare (popmax 0.0011%, sas).

How common is RASGRP2 p.Ile427= (c.1281C>T) in the general population?

RASGRP2 p.Ile427= (c.1281C>T) is very rare (popmax 0.0011%, sas) (gnomAD).

RASGRP2 p.Ile427=

c.1281C>T · rs907671862 · VCV2882030

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.0011%, sas)

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 -5.1	GERP -3.6
Overall
CADD	0.488	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0011% South Asian · 1/91,088 alleles

Filtering AF 7.9e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 5.4e-05%

Overall 0.000434% 7/1,614,042 alleles · very rare exomes 7/1,461,770 · genomes 0/152,272 · joint denominator

Ancestry group	Frequency	1 in
Remaining individualsnot grpmax-eligible	0.0032%	31,254
South Asiangrpmax	0.0011%	91,088
European (non-Finnish)	0.000339%	294,993

Remaining individuals shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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: RASGRP2
Protein: p.Ile427=
Coding: c.1281C>T
MANE Select: NM_001098671
dbSNP: rs907671862
Type: single nucleotide variant
Location: chr11:64735557 (GRCh38)
Gene constraint: LOEUF 0.854 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 77.48 · 2 PDB
Residue 427: 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); the ef-hand 1 domain; an α-helix

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

Similar variants

RASGRP2 p.Ile427Met Uncertain significance ★ ⚠ same residue
RASGRP2 p.Ile427Val Uncertain significance ★ ⚠ same residue
RASGRP2 p.Gly305Asp Likely pathogenic ★★ same type
RASGRP2 p.Arg387Gly Uncertain significance ★★ ⚠ same type
RASGRP2 p.Arg593His Uncertain significance ★★ ⚠ same type
RASGRP2 p.Asn330Lys Uncertain significance ★★ ⚠ same type
RASGRP2 p.Gly331Arg Uncertain significance ★★ ⚠ same type
RASGRP2 p.Gly492Trp Uncertain significance ★★ ⚠ 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/rasgrp2-p-ile427 (accessed [today's date]).

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