Is MET p.Ser615fs (c.1845_1848del) pathogenic?

MET p.Ser615fs (c.18451848del) is classified Uncertain significance in MET (ClinVar, Single submitter, 1 submitter; last evaluated 2025-12-11). Associated with hereditary neoplastic syndrome.

What condition is associated with MET p.Ser615fs (c.1845_1848del)?

MET p.Ser615fs (c.1845_1848del) is associated with hereditary neoplastic syndrome (ClinVar).

MET p.Ser615fs

c.1845_1848del · VCV4647066

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

Conditions

hereditary neoplastic syndrome

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 6 of 21
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 1.8	GERP -2, phastCons 1

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

Variant & gene context

Gene: MET
Protein: p.Ser615fs
Coding: c.1845_1848del
MANE Select: NM_000245
Type: Deletion
Location: chr7:116755496 (GRCh38)
Gene constraint: LOEUF 0.446 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 79.28 · 130 PDB
Residue 615: an α-helix; the ipt/tig 1 domain

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

Disease context

hereditary neoplastic syndrome — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

MET c.2265-42del Uncertain significance ★★ same condition
MET p.Gly1119del Uncertain significance ★★ same condition
MET p.His1052fs Uncertain significance ★★ same condition
MET p.Leu893fs 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
MET p.Ser653del 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-ser615fs (accessed [today's date]).

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