Is MET p.Ser653del (c.1958_1960del) pathogenic?

MET p.Ser653del (c.19581960del) is classified Uncertain significance in MET (ClinVar, Multiple submitters, 2 submitters; last evaluated 2022-01-14). Absent from gnomAD; Associated with hereditary neoplastic syndrome.

What condition is associated with MET p.Ser653del (c.1958_1960del)?

MET p.Ser653del (c.1958_1960del) is associated with hereditary neoplastic syndrome, renal cell carcinoma (ClinVar).

How common is MET p.Ser653del (c.1958_1960del) in the general population?

MET p.Ser653del (c.1958_1960del) is absent from gnomAD (gnomAD).

MET p.Ser653del

c.1958_1960del · rs1430652609 · VCV834421

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Not reported

no gnomAD frequency available for this variant

Conditions

hereditary neoplastic syndrome

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 7.9	GERP 1.6, phastCons 1

Population frequency

dbSNP / gnomAD

No gnomAD frequency available for this variant. This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: MET
Protein: p.Ser653del
Coding: c.1958_1960del
MANE Select: NM_024755 · reported on NM_000245
dbSNP: rs1430652609
Type: Deletion
Location: chr7:116757530 (GRCh38)
Structure: AlphaFold pLDDT 52.38

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

Also linked: renal cell carcinoma

Similar variants

MET p.Ser653Phe Uncertain significance ★★ ⚠ same residue
MET p.Ser653= 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.Leu893fs Uncertain significance ★★ same condition
MET p.Met1fs Uncertain significance ★★ same condition
MET p.Phe258fs 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-ser653del (accessed [today's date]).

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