Is MET p.Leu893fs (c.2676_2680del) pathogenic?

MET p.Leu893fs (c.26762680del) is classified Uncertain significance in MET (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-05-18). Associated with renal cell carcinoma.

What condition is associated with MET p.Leu893fs (c.2676_2680del)?

MET p.Leu893fs (c.2676_2680del) is associated with renal cell carcinoma, hereditary neoplastic syndrome (ClinVar).

MET p.Leu893fs

c.2676_2680del · VCV3395099

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

Conditions

renal cell carcinoma

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function; NMD-escape possible for C-terminal truncations
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 4.4	GERP 0.92, phastCons 1

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

Variant & gene context

Gene: MET
Protein: p.Leu893fs
Coding: c.2676_2680del
MANE Select: NM_024755 · reported on NM_000245
Type: Deletion
Location: chr7:116769736 (GRCh38)
Structure: AlphaFold pLDDT 52.38
Residue 893: the 'disordered' region

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

Disease context

renal cell carcinoma — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: hereditary neoplastic syndrome

Similar variants

MET p.Leu893Ile Conflicting classifications of pathogenicity ★ ⚠ same residue
MET p.Leu893= Likely benign ★ same residue
MET c.2265-42del Uncertain significance ★★ same condition
MET p.Gly1119del Uncertain significance ★★ same condition
MET p.His1052fs Uncertain significance ★★ same condition
MET p.Met1fs Uncertain significance ★★ same condition
MET p.Phe258fs Uncertain significance ★★ same condition
MET p.Pro356fs 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/met-p-leu893fs (accessed [today's date]).

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