Is MAP2K2 p.Ile97del (c.288CAT[1]) pathogenic?

MAP2K2 p.Ile97del (c.288CAT[1]) is classified Uncertain significance in MAP2K2 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2026-01-19). Very rare (popmax 0.000169%, nfe); Associated with RASopathy.

What condition is associated with MAP2K2 p.Ile97del (c.288CAT[1])?

MAP2K2 p.Ile97del (c.288CAT[1]) is associated with RASopathy, cardiofaciocutaneous syndrome 4 (ClinVar).

How common is MAP2K2 p.Ile97del (c.288CAT[1]) in the general population?

MAP2K2 p.Ile97del (c.288CAT[1]) is very rare (popmax 0.000169%, nfe) (gnomAD).

MAP2K2 p.Ile97del

c.288CAT[1] · rs1555698652 · VCV543989

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

gnomAD v4.1

Rare

very rare (popmax 0.000169%, nfe)

Conditions

RASopathy

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 7.6	GERP 1.9, phastCons 1

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.000169% European (non-Finnish) · 2/1,180,028 alleles

Filtering AF 2.8e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.1e-05%

Overall 0.000124% 2/1,613,298 alleles · very rare exomes 2/1,460,950 · genomes 0/152,348 · 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.Ile97del
Coding: c.288CAT[1]
MANE Select: NM_030662
dbSNP: rs1555698652
Type: Microsatellite
Location: chr19:4117429 (GRCh38)
Gene constraint: LOEUF 0.858 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 82.54 · 3 PDB
Residue 97: the protein kinase domain; a β-strand

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

Disease context

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

Also linked: cardiofaciocutaneous syndrome 4

Similar variants

MAP2K2 p.Ile97Met Conflicting classifications of pathogenicity ★ ⚠ same residue
MAP2K2 p.Ile97Phe Conflicting classifications of pathogenicity ★ ⚠ same residue
MAP2K2 p.Ile97= Likely benign ★ same residue
MAP2K2 p.Ile325fs Uncertain significance ★★ same condition
MAP2K2 c.985-7_985-5del Likely benign ★★ same condition
MAP2K2 p.Glu288del Conflicting classifications of pathogenicity ★ same condition
MAP2K2 p.Lys52del Uncertain significance ★ same condition
MAP2K2 c.451-20_451-17del Likely benign ★ 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-ile97del (accessed [today's date]).

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