Is MET p.Arg412fs (c.1233_1236del) pathogenic?

MET p.Arg412fs (c.12331236del) is classified Uncertain significance in MET (ClinVar, Single submitter, 1 submitter; last evaluated 2024-10-28). Associated with renal cell carcinoma.

What condition is associated with MET p.Arg412fs (c.1233_1236del)?

MET p.Arg412fs (c.1233_1236del) is associated with renal cell carcinoma (ClinVar).

MET p.Arg412fs

c.1233_1236del · VCV3723912

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

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 in a LoF-intolerant gene
NMD	predicted	premature termination codon in exon 3 of 21
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 4.7	GERP 0.48, phastCons 1

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

Variant & gene context

Gene: MET
Protein: p.Arg412fs
Coding: c.1233_1236del
MANE Select: NM_000245
Type: Microsatellite
Location: chr7:116731698 (GRCh38)
Gene constraint: LOEUF 0.446 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 79.28 · 130 PDB
Residue 412: the sema domain

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

Similar variants

MET p.Arg412Cys Conflicting classifications of pathogenicity ★ ⚠ same residue
MET p.Arg412His Conflicting classifications of pathogenicity ★ ⚠ same residue
MET p.Arg412Leu Uncertain significance ★ ⚠ same residue
MET p.Ser204del Uncertain significance ★★ same condition
MET c.2888-12_2888-9del Likely benign ★★ same condition
MET c.2888-16_2888-13del Likely benign ★★ same condition
MET c.3523-16CT[2] Likely benign ★★ same condition
MET c.3936-13_3936-10del Conflicting classifications of pathogenicity ★ 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-arg412fs (accessed [today's date]).

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