Is MAP2K1 p.Pro266del (c.792TCC[1]) pathogenic?

MAP2K1 p.Pro266del (c.792TCC[1]) is classified Uncertain significance in MAP2K1 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-04-06). Very rare (popmax 0.000254%, nfe); Associated with RASopathy.

What condition is associated with MAP2K1 p.Pro266del (c.792TCC[1])?

MAP2K1 p.Pro266del (c.792TCC[1]) is associated with RASopathy (ClinVar).

How common is MAP2K1 p.Pro266del (c.792TCC[1]) in the general population?

MAP2K1 p.Pro266del (c.792TCC[1]) is very rare (popmax 0.000254%, nfe) (gnomAD).

MAP2K1 p.Pro266del

c.792TCC[1] · VCV3716737

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.000254%, 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 1.1	GERP 2, phastCons 1

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.000254% European (non-Finnish) · 3/1,179,908 alleles

Filtering AF 6.8e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.9e-05%

Overall 0.000186% 3/1,613,868 alleles · very rare exomes 3/1,461,590 · genomes 0/152,278 · 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: MAP2K1
Protein: p.Pro266del
Coding: c.792TCC[1]
MANE Select: NM_002755
Type: Microsatellite
Location: chr15:66485086 (GRCh38)
Gene constraint: LOEUF 0.515 · pLI 0.97 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 84.05 · 99 PDB
Residue 266: the protein kinase domain; an α-helix

Full MAP2K1 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

MAP2K1 p.Pro266Ser Uncertain significance ★★ ⚠ same residue
MAP2K1 c.1068+12_1068+15del Benign ★★★ same condition
MAP2K1 c.694-12TC[4] Benign ★★★ same condition
MAP2K1 c.568+6_568+8del Uncertain significance ★ same condition
MAP2K1 p.Asp43del Uncertain significance ★ same condition
MAP2K1 c.438+16_438+17del Likely benign ★ same condition
MAP2K1 c.694-13_694-10del Likely benign ★ same condition
MAP2K1 c.961-8_961-7del 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/map2k1-p-pro266del (accessed [today's date]).

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