Is MAP2K2 p.Tyr233= (c.699C>T) pathogenic?

MAP2K2 p.Tyr233= (c.699C>T) is classified Likely benign in MAP2K2 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2023-12-16). Very rare (popmax 0.00136%, afr); Associated with Cardiovascular phenotype.

What condition is associated with MAP2K2 p.Tyr233= (c.699C>T)?

MAP2K2 p.Tyr233= (c.699C>T) is associated with Cardiovascular phenotype, RASopathy (ClinVar).

How common is MAP2K2 p.Tyr233= (c.699C>T) in the general population?

MAP2K2 p.Tyr233= (c.699C>T) is very rare (popmax 0.00136%, afr) (gnomAD).

MAP2K2 p.Tyr233=

c.699C>T · rs1044588100 · VCV632880

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

gnomAD v4.1

Rare

very rare (popmax 0.00136%, afr)

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 5.9	GERP 1.9, phastCons 1
Overall
CADD	6.935	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00136% African / African-American · 1/73,314 alleles

Overall 6.41e-05% 1/1,558,932 alleles · very rare exomes 0/1,406,818 · genomes 1/152,114 · 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.Tyr233=
Coding: c.699C>T
MANE Select: NM_030662
dbSNP: rs1044588100
Type: single nucleotide variant
Location: chr19:4101025 (GRCh38)
Gene constraint: LOEUF 0.858 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 82.54 · 3 PDB
Residue 233: 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

Also linked: RASopathy

Similar variants

MAP2K2 p.Glu207Lys Likely pathogenic ★★★ same condition
MAP2K2 p.Phe57Cys Pathogenic ★★★ same condition
MAP2K2 p.Pro128Gln Pathogenic ★★★ same condition
MAP2K2 p.Tyr134Cys Likely pathogenic ★★★ same condition
MAP2K2 p.Tyr134His Pathogenic ★★★ same condition
MAP2K2 p.Arg231His Uncertain significance ★★★ ⚠ same condition
MAP2K2 p.Arg231Leu Uncertain significance ★★★ ⚠ same condition
MAP2K2 p.Arg281Gln 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-tyr233 (accessed [today's date]).

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