Is RASGRP2 p.Met41Val (c.121A>G) pathogenic?

RASGRP2 p.Met41Val (c.121A>G) is classified Uncertain significance in RASGRP2 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-09-26). AlphaMissense: ambiguous (0.4231); Absent from gnomAD v4.1; Associated with Inborn genetic diseases.

What condition is associated with RASGRP2 p.Met41Val (c.121A>G)?

RASGRP2 p.Met41Val (c.121A>G) is associated with Inborn genetic diseases (ClinVar).

How common is RASGRP2 p.Met41Val (c.121A>G) in the general population?

RASGRP2 p.Met41Val (c.121A>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about RASGRP2 p.Met41Val (c.121A>G)?

AlphaMissense predicts ambiguous (score 0.4231) — an in-silico prediction, not a clinical call.

RASGRP2 p.Met41Val

c.121A>G · VCV3430652

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.4231 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/2 damaging

REVEL, SaProt · AlphaMissense no call

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.4231	ambiguous
REVEL	0.224	benign-leaning
SaProt	LLR -5.15	tolerated
⇒ REVEL and SaProt both call this tolerated; AlphaMissense makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.7	GERP -1.4, phastCons 1
Regional constraint	o/e 0.82	unconstrained · MANE · 16 kb · p 1.3e-07 · regional, not allelic
Overall
CADD	23.8	PHRED · no single calibrated threshold — expert panels disagree

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: RASGRP2
Protein: p.Met41Val
Coding: c.121A>G
MANE Select: NM_001098671
Type: single nucleotide variant
Location: chr11:64742065 (GRCh38)
Gene constraint: LOEUF 0.854 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 77.48 · 2 PDB
Residue 41: the n-terminal ras-gef domain; an α-helix

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

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

RASGRP2 p.Arg593His Uncertain significance ★★ ⚠ same condition
RASGRP2 p.Gly492Trp Uncertain significance ★★ ⚠ same condition
RASGRP2 p.Lys55Met Uncertain significance ★★ same condition
RASGRP2 p.Thr396Met Uncertain significance ★★ ⚠ same condition
RASGRP2 p.Ala414Thr Uncertain significance ★ ⚠ same condition
RASGRP2 p.Ala517Ser Uncertain significance ★ ⚠ same condition
RASGRP2 p.Arg113Gln Uncertain significance ★ ⚠ same condition
RASGRP2 p.Arg131Gln Uncertain significance ★ ⚠ 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-met41val (accessed [today's date]).

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