Is MAP2K2 p.Leu350Arg (c.1049T>G) pathogenic?

MAP2K2 p.Leu350Arg (c.1049T>G) is classified Uncertain significance in MAP2K2 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-09-26). AlphaMissense: likely pathogenic (0.9887); Absent from gnomAD v4.1.

How common is MAP2K2 p.Leu350Arg (c.1049T>G) in the general population?

MAP2K2 p.Leu350Arg (c.1049T>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about MAP2K2 p.Leu350Arg (c.1049T>G)?

AlphaMissense predicts likely pathogenic (score 0.9887) — an in-silico prediction, not a clinical call.

MAP2K2 p.Leu350Arg

c.1049T>G · VCV3774802

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9887 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.9887	likely pathogenic
REVEL	0.828	moderately pathogenic-leaning
SaProt	LLR -9.97	tolerated
⇒ AlphaMissense and REVEL call this damaging; SaProt does not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 11	GERP 1.7, phastCons 1
Regional constraint	o/e 0.96	unconstrained · MANE · 8,766 bp · p 0.55 · regional, not allelic
Overall
CADD	31.0	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: MAP2K2
Protein: p.Leu350Arg
Coding: c.1049T>G
MANE Select: NM_030662
Type: single nucleotide variant
Location: chr19:4094496 (GRCh38)
Gene constraint: LOEUF 0.858 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 82.54 · 3 PDB
Residue 350: the protein kinase domain

Full MAP2K2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

MAP2K2 p.Leu350= Likely benign ★★ same residue
MAP2K2 p.Glu207Lys Likely pathogenic ★★★ same type
MAP2K2 p.Phe57Cys Pathogenic ★★★ same type
MAP2K2 p.Phe57Val Pathogenic ★★★ same type
MAP2K2 p.Pro128Gln Pathogenic ★★★ same type
MAP2K2 p.Tyr134Cys Likely pathogenic ★★★ same type
MAP2K2 p.Tyr134His Pathogenic ★★★ same type
MAP2K2 p.Arg231His 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/map2k2-p-leu350arg (accessed [today's date]).

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