Is MET p.Phe736fs (c.2204dup) pathogenic?

MET p.Phe736fs (c.2204dup) is classified Uncertain significance in MET (ClinVar, Single submitter, 1 submitter; last evaluated 2021-10-15). No gnomAD frequency available for this variant; Associated with renal cell carcinoma.

What condition is associated with MET p.Phe736fs (c.2204dup)?

MET p.Phe736fs (c.2204dup) is associated with renal cell carcinoma (ClinVar).

How common is MET p.Phe736fs (c.2204dup) in the general population?

MET p.Phe736fs (c.2204dup) is no gnomAD frequency available for this variant (gnomAD).

MET p.Phe736fs

c.2204dup · rs2116931908 · VCV1461578

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Not reported

no gnomAD frequency available for this variant

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 9 of 21
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 4.2	GERP 1.7, phastCons 1

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

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.Phe736fs
Coding: c.2204dup
MANE Select: NM_000245
dbSNP: rs2116931908
Type: Duplication
Location: chr7:116758559 (GRCh38)
Gene constraint: LOEUF 0.446 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 79.28 · 130 PDB
Residue 736: a β-strand; the ipt/tig 2 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.Glu873Ter Uncertain significance ★★ same condition
MET c.1393-10dup Benign/Likely benign ★★ same condition
MET c.1863-5dup Benign/Likely benign ★★ same condition
MET c.2103-7dup Benign/Likely benign ★★ same condition
MET c.3340+2dup Uncertain significance ★ same condition
MET p.Gln433fs Uncertain significance ★ same condition
MET p.Ile193_Asn194insValLeuSerSerValLysAspArgPheIle Uncertain significance ★ same condition
MET p.Pro9fs 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-phe736fs (accessed [today's date]).

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