Is MAPK1 p.Met1fs (c.-12_11del) pathogenic?

MAPK1 p.Met1fs (c.-1211del) is classified Uncertain significance in MAPK1 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-07-14). Very rare (popmax 0.000108%, nfe).

How common is MAPK1 p.Met1fs (c.-12_11del) in the general population?

MAPK1 p.Met1fs (c.-12_11del) is very rare (popmax 0.000108%, nfe) (gnomAD).

MAPK1 p.Met1fs

c.-12_11del · VCV4947107

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.000108%, nfe)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function in a LoF-intolerant gene
NMD	predicted	premature termination codon in exon 1 of 9
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 0.29	GERP 1.8, phastCons 0.97
Region caveats
Repeat context	tandem	(CCG)n simple repeat · ambiguous alignment · confidence, not pathogenicity

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.000108% European (non-Finnish) · 1/927,128 alleles

Overall 8.78e-05% 1/1,138,764 alleles · very rare exomes 1/989,324 · genomes 0/149,440 · 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: MAPK1
Protein: p.Met1fs
Coding: c.-12_11del
MANE Select: NM_002745
Type: Deletion
Location: chr22:21867430 (GRCh38)
Gene constraint: LOEUF 0.377 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 90.99 · 157 PDB

Full MAPK1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

MAPK1 c.967-15del Likely benign ★ same type

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/mapk1-p-met1fs (accessed [today's date]).

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