Is MET p.Pro1283Ser (c.3847C>T) pathogenic?

MET p.Pro1283Ser (c.3847C>T) is classified Uncertain significance in MET (ClinVar, Multiple submitters, 2 submitters; last evaluated 2024-05-08). AlphaMissense: likely pathogenic (0.9918); Absent from gnomAD v4.1; Associated with renal cell carcinoma.

What condition is associated with MET p.Pro1283Ser (c.3847C>T)?

MET p.Pro1283Ser (c.3847C>T) is associated with renal cell carcinoma, hereditary neoplastic syndrome (ClinVar).

How common is MET p.Pro1283Ser (c.3847C>T) in the general population?

MET p.Pro1283Ser (c.3847C>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about MET p.Pro1283Ser (c.3847C>T)?

AlphaMissense predicts likely pathogenic (score 0.9918) — an in-silico prediction, not a clinical call.

MET p.Pro1283Ser

c.3847C>T · rs1795646988 · VCV2587473

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely pathogenic

0.9918 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

renal cell carcinoma

Computational evidence

Protein change
AlphaMissense	0.9918	likely pathogenic · top 6% in MET
REVEL	0.913	moderately pathogenic-leaning
SaProt	LLR -9.04	tolerated
⇒ AlphaMissense and REVEL call this damaging; SaProt does not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.7	GERP 1.8, phastCons 1
Overall
CADD	27.8	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: MET
Protein: p.Pro1283Ser
Coding: c.3847C>T
MANE Select: NM_000245
dbSNP: rs1795646988
Type: single nucleotide variant
Location: chr7:116795703 (GRCh38)
Gene constraint: LOEUF 0.446 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 79.28 · 130 PDB
Residue 1283: the 'interaction with ranbp9' region; a β-strand; the protein kinase 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

Also linked: hereditary neoplastic syndrome

Similar variants

MET p.Pro1283= Likely benign ★ same residue
MET p.His1094Arg Pathogenic/Likely pathogenic ★★ ⚠ same condition
MET p.Met1131Thr Pathogenic/Likely pathogenic ★★ same condition
MET p.Val1092Ile Pathogenic/Likely pathogenic ★★ same condition
MET p.Val1220Ile Pathogenic/Likely pathogenic ★★ same condition
MET c.1200+2T>C Uncertain significance ★★ same condition
MET c.1392+1G>T Uncertain significance ★★ same condition
MET c.1392+3A>G 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-pro1283ser (accessed [today's date]).

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