Is RASGRP2 p.Ser50Phe (c.149C>T) pathogenic?

RASGRP2 p.Ser50Phe (c.149C>T) is classified Uncertain significance in RASGRP2 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-08-05). AlphaMissense: likely benign (0.301); Absent from gnomAD v4.1; Associated with Inborn genetic diseases.

What condition is associated with RASGRP2 p.Ser50Phe (c.149C>T)?

RASGRP2 p.Ser50Phe (c.149C>T) is associated with Inborn genetic diseases (ClinVar).

How common is RASGRP2 p.Ser50Phe (c.149C>T) in the general population?

RASGRP2 p.Ser50Phe (c.149C>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about RASGRP2 p.Ser50Phe (c.149C>T)?

AlphaMissense predicts likely benign (score 0.301) — an in-silico prediction, not a clinical call.

RASGRP2 p.Ser50Phe

c.149C>T · VCV4150930

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.301 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.301	likely benign
REVEL	0.2	benign-leaning
SaProt	LLR -10.19	damaging
⇒ SaProt calls this damaging; AlphaMissense and REVEL do not.
Splicing
SpliceAI	Δ0.35	acceptor gain · deltas
Pangolin	Δ0.25	gain · loss 0.12 · agrees with SpliceAI · independent
Constraint at this position
Conservation	phyloP 12	GERP 1.8, phastCons 1
Regional constraint	o/e 0.82	unconstrained · MANE · 16 kb · p 1.3e-07 · regional, not allelic
Overall
CADD	34.0	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.Ser50Phe
Coding: c.149C>T
MANE Select: NM_001098671
Type: single nucleotide variant
Location: chr11:64742037 (GRCh38)
Gene constraint: LOEUF 0.854 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 77.48 · 2 PDB
Residue 50: 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-ser50phe (accessed [today's date]).

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