Is MAP2K2 p.Thr386= (c.1158C>T) pathogenic?

MAP2K2 p.Thr386= (c.1158C>T) is classified Likely benign in MAP2K2 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-12-27). Absent from gnomAD v4.1; Associated with RASopathy.

What condition is associated with MAP2K2 p.Thr386= (c.1158C>T)?

MAP2K2 p.Thr386= (c.1158C>T) is associated with RASopathy (ClinVar).

How common is MAP2K2 p.Thr386= (c.1158C>T) in the general population?

MAP2K2 p.Thr386= (c.1158C>T) is absent from gnomAD v4.1 (gnomAD).

MAP2K2 p.Thr386=

c.1158C>T · rs865940003 · VCV2727134

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Absent

absent from gnomAD v4.1

Conditions

RASopathy

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 -0.061	GERP -2.4, phastCons 0.43
Overall
CADD	5.503	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: MAP2K2
Protein: p.Thr386=
Coding: c.1158C>T
MANE Select: NM_030662
dbSNP: rs865940003
Type: single nucleotide variant
Location: chr19:4090643 (GRCh38)
Gene constraint: LOEUF 0.858 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 82.54 · 3 PDB
Residue 386: an α-helix

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.Thr386Asn Uncertain significance ★ same residue
MAP2K2 p.Thr386Ile Uncertain significance ★ ⚠ same residue
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

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-thr386 (accessed [today's date]).

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