Is MAP2K2 p.Gln247= (c.741G>A) pathogenic?

MAP2K2 p.Gln247= (c.741G>A) is classified Likely benign in MAP2K2 (ClinVar, Single submitter, 2 submitters; last evaluated 2021-04-08). Very rare (popmax 0.000594%, nfe); Associated with Cardiovascular phenotype.

What condition is associated with MAP2K2 p.Gln247= (c.741G>A)?

MAP2K2 p.Gln247= (c.741G>A) is associated with Cardiovascular phenotype (ClinVar).

How common is MAP2K2 p.Gln247= (c.741G>A) in the general population?

MAP2K2 p.Gln247= (c.741G>A) is very rare (popmax 0.000594%, nfe) (gnomAD).

MAP2K2 p.Gln247=

c.741G>A · rs2040968312 · VCV1758835

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

very rare (popmax 0.000594%, nfe)

Conditions

Cardiovascular phenotype

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 3.3	GERP 1.8, phastCons 1
Overall
CADD	13.53	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.000594% European (non-Finnish) · 7/1,179,266 alleles

Filtering AF 0.000247% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000159%

Overall 0.000434% 7/1,611,484 alleles · very rare exomes 6/1,459,238 · genomes 1/152,246 · joint denominator

Rarity supports pathogenicity (ACMG PM2); frequency above a disease-specific BA1/BS1 threshold argues against it. A variant frequent in one ancestry group can be near-absent in others, so a single global figure can mislead.

Variant & gene context

Gene: MAP2K2
Protein: p.Gln247=
Coding: c.741G>A
MANE Select: NM_030662
dbSNP: rs2040968312
Type: single nucleotide variant
Location: chr19:4099379 (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.Gln247Arg Uncertain significance ★ ⚠ 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-gln247 (accessed [today's date]).

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