Is MAP2K2 p.Arg397= (c.1191C>A) pathogenic?

MAP2K2 p.Arg397= (c.1191C>A) is classified Likely benign in MAP2K2 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2024-05-08). Absent from gnomAD v4.1; Associated with MAP2K2-related disorder.

What condition is associated with MAP2K2 p.Arg397= (c.1191C>A)?

MAP2K2 p.Arg397= (c.1191C>A) is associated with MAP2K2-related disorder (ClinVar).

How common is MAP2K2 p.Arg397= (c.1191C>A) in the general population?

MAP2K2 p.Arg397= (c.1191C>A) is absent from gnomAD v4.1 (gnomAD).

MAP2K2 p.Arg397=

c.1191C>A · VCV3348051

Likely benign No assertion criteria

Classification

Likely benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Absent

absent from gnomAD v4.1

Conditions

MAP2K2-related disorder

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 0.32	GERP -3.2, phastCons 0.39
Overall
CADD	3.37	PHRED · no single calibrated threshold — expert panels disagree

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.Arg397=
Coding: c.1191C>A
MANE Select: NM_030662
Type: single nucleotide variant
Location: chr19:4090610 (GRCh38)
Gene constraint: LOEUF 0.858 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 82.54 · 3 PDB

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

Disease context

MAP2K2-related disorder

Similar variants

MAP2K2 p.Arg397His Uncertain significance ★★ ⚠ same residue
MAP2K2 p.Arg397Cys Conflicting classifications of pathogenicity ★ ⚠ same residue
MAP2K2 p.Arg397Leu Uncertain significance ★ ⚠ same residue
MAP2K2 p.Pro128Leu Pathogenic/Likely pathogenic ★★ same condition
MAP2K2 p.Glu118Lys Uncertain significance ★★ ⚠ same condition
MAP2K2 p.Gly214Arg Uncertain significance ★★ ⚠ same condition
MAP2K2 p.Lys348Arg Uncertain significance ★★ ⚠ same condition
MAP2K2 p.Ala62Pro Likely pathogenic ★ 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/map2k2-p-arg397 (accessed [today's date]).

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