Is MAP2K2 p.Thr396fs (c.1185del) pathogenic?

MAP2K2 p.Thr396fs (c.1185del) is classified Uncertain significance in MAP2K2 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-07-06). No gnomAD frequency available for this variant; Associated with RASopathy.

What condition is associated with MAP2K2 p.Thr396fs (c.1185del)?

MAP2K2 p.Thr396fs (c.1185del) is associated with RASopathy (ClinVar).

How common is MAP2K2 p.Thr396fs (c.1185del) in the general population?

MAP2K2 p.Thr396fs (c.1185del) is no gnomAD frequency available for this variant (gnomAD).

MAP2K2 p.Thr396fs

c.1185del · rs2040845949 · VCV1037390

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Not reported

no gnomAD frequency available for this variant

Conditions

RASopathy

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function
NMD	escapes	premature termination codon in the last exon (11 of 11) — the truncated protein is likely expressed. PVS1 input, not an applied code
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 7.6	GERP 1.9, phastCons 1

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

dbSNP / gnomAD

No gnomAD frequency available for this variant. 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.Thr396fs
Coding: c.1185del
MANE Select: NM_030662
dbSNP: rs2040845949
Type: Deletion
Location: chr19:4090616 (GRCh38)
Gene constraint: LOEUF 0.858 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 82.54 · 3 PDB
Residue 396: a modified residue (phosphothreonine)

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

Similar variants

MAP2K2 p.Thr396Met Uncertain significance ★★★ ⚠ same residue
MAP2K2 p.Thr396= Likely benign ★ same residue
MAP2K2 p.Leu54fs Uncertain significance ★★ same condition
MAP2K2 c.303+15del Benign/Likely benign ★★ same condition
MAP2K2 c.1046+5_1046+8del Uncertain significance ★ same condition
MAP2K2 c.1046+5del Uncertain significance ★ same condition
MAP2K2 c.578_580+9del Uncertain significance ★ same condition
MAP2K2 p.Ala162fs 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-thr396fs (accessed [today's date]).

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