Is RASGRP2 p.Pro267= (c.801T>A) pathogenic?

RASGRP2 p.Pro267= (c.801T>A) is classified Likely benign in RASGRP2 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-12-15). Very rare (popmax 0.000339%, nfe).

How common is RASGRP2 p.Pro267= (c.801T>A) in the general population?

RASGRP2 p.Pro267= (c.801T>A) is very rare (popmax 0.000339%, nfe) (gnomAD).

RASGRP2 p.Pro267=

c.801T>A · rs754141015 · VCV2909582

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.000339%, nfe)

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 -5.6	GERP -3.6
Overall
CADD	1.848	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.000339% European (non-Finnish) · 4/1,179,692 alleles

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

Overall 0.00186% 30/1,613,672 alleles · very rare exomes 24/1,461,520 · genomes 6/152,152 · joint denominator

Ancestry group	Frequency	1 in
Ashkenazi Jewishnot grpmax-eligible	0.0844%	1,184
Remaining individualsnot grpmax-eligible	0.0016%	62,482
European (non-Finnish)grpmax	0.000339%	294,923

Ashkenazi Jewish 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.Pro267=
Coding: c.801T>A
MANE Select: NM_001098671
dbSNP: rs754141015
Type: single nucleotide variant
Location: chr11:64739372 (GRCh38)
Gene constraint: LOEUF 0.854 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 77.48 · 2 PDB
Residue 267: the ras-gef domain; 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); an α-helix

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

Similar variants

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
RASGRP2 p.Leu107Ile Uncertain significance ★★ ⚠ same type
RASGRP2 p.Lys55Met 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-pro267 (accessed [today's date]).

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