Is MAP2K2 p.Val228= (c.684G>A) pathogenic?

MAP2K2 p.Val228= (c.684G>A) is classified Likely benign in MAP2K2 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-10-07). No allele count reported in gnomAD v4.1 (AN 1,569,304); Associated with Cardiovascular phenotype.

What condition is associated with MAP2K2 p.Val228= (c.684G>A)?

MAP2K2 p.Val228= (c.684G>A) is associated with Cardiovascular phenotype (ClinVar).

How common is MAP2K2 p.Val228= (c.684G>A) in the general population?

MAP2K2 p.Val228= (c.684G>A) is no allele count reported in gnomAD v4.1 (AN 1,569,304) (gnomAD).

MAP2K2 p.Val228=

c.684G>A · rs961138933 · VCV1755785

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 1,569,304)

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 0.08	GERP 0.8, phastCons 0.92
Overall
CADD	7.087	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

No allele count reported in gnomAD v4.1 (AN 1,569,304). This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: MAP2K2
Protein: p.Val228=
Coding: c.684G>A
MANE Select: NM_030662
dbSNP: rs961138933
Type: single nucleotide variant
Location: chr19:4101040 (GRCh38)
Gene constraint: LOEUF 0.858 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 82.54 · 3 PDB
Residue 228: the protein kinase domain

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.Val228Met Uncertain significance ★★ ⚠ same residue
MAP2K2 p.Val228Leu 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
MAP2K2 p.Arg193Gln 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-val228 (accessed [today's date]).

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