Is MAP2K2 p.Gln247Arg (c.740A>G) pathogenic?

MAP2K2 p.Gln247Arg (c.740A>G) is classified Uncertain significance in MAP2K2 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-07-09). AlphaMissense: likely pathogenic (0.7033); Absent from gnomAD v4.1; Associated with Cardiovascular phenotype.

What condition is associated with MAP2K2 p.Gln247Arg (c.740A>G)?

MAP2K2 p.Gln247Arg (c.740A>G) is associated with Cardiovascular phenotype (ClinVar).

How common is MAP2K2 p.Gln247Arg (c.740A>G) in the general population?

MAP2K2 p.Gln247Arg (c.740A>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about MAP2K2 p.Gln247Arg (c.740A>G)?

AlphaMissense predicts likely pathogenic (score 0.7033) — an in-silico prediction, not a clinical call.

MAP2K2 p.Gln247Arg

c.740A>G · VCV4103131

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.7033 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

Cardiovascular phenotype

Computational evidence

Protein change
AlphaMissense	0.7033	likely pathogenic
REVEL	0.599	indeterminate
SaProt	LLR -10.94	damaging
⇒ AlphaMissense and SaProt both call this damaging; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.9	GERP 0.94, phastCons 1
Regional constraint	o/e 0.67	unconstrained · MANE · 18 kb · p 1.4e-08 · regional, not allelic
Overall
CADD	26.6	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — a triage signal, not a reclassification

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.Gln247Arg
Coding: c.740A>G
MANE Select: NM_030662
Type: single nucleotide variant
Location: chr19:4099380 (GRCh38)
Gene constraint: LOEUF 0.858 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 82.54 · 3 PDB
Residue 247: the protein kinase domain; an α-helix

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

Disease context

Cardiovascular phenotype — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

MAP2K2 p.Gln247= Likely benign ★ same residue
MAP2K2 p.Gln247Pro Uncertain significance ★★ ⚠ same residue
MAP2K2 p.Gln247Ter Uncertain significance ★ same residue
MAP2K2 p.Gly132Asp Pathogenic/Likely pathogenic ★★ same condition
MAP2K2 c.450+5G>A Uncertain significance ★★ same condition
MAP2K2 p.Ala355Val Uncertain significance ★★ ⚠ same condition
MAP2K2 p.Ala358Val Uncertain significance ★★ ⚠ same condition
MAP2K2 p.Ala380Val 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/map2k2-p-gln247arg (accessed [today's date]).

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