Is MET p.Pro475= (c.1425T>A) pathogenic?

MET p.Pro475= (c.1425T>A) is classified Benign/Likely benign in MET (ClinVar, Multiple submitters, 3 submitters; last evaluated 2025-07-01). Absent from gnomAD v4.1; Associated with hereditary neoplastic syndrome.

What condition is associated with MET p.Pro475= (c.1425T>A)?

MET p.Pro475= (c.1425T>A) is associated with hereditary neoplastic syndrome, renal cell carcinoma (ClinVar).

How common is MET p.Pro475= (c.1425T>A) in the general population?

MET p.Pro475= (c.1425T>A) is absent from gnomAD v4.1 (gnomAD).

MET p.Pro475=

c.1425T>A · rs2116826219 · VCV1772369

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

gnomAD v4.1

Absent

absent from gnomAD v4.1

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 · no allele here is in the release
Constraint at this position
Conservation	phyloP -0.4	GERP -0.83, phastCons 0.2
Overall
CADD	6.875	PHRED · no single calibrated threshold — expert panels disagree

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.Pro475=
Coding: c.1425T>A
MANE Select: NM_024755 · reported on NM_000245
dbSNP: rs2116826219
Type: single nucleotide variant
Location: chr7:116739982 (GRCh38)
Structure: AlphaFold pLDDT 52.38
Residue 475: the 'disordered' region

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.Pro475Arg Uncertain significance ★★ ⚠ same residue
MET p.Pro475Leu Uncertain significance ★★ ⚠ same residue
MET p.Pro475Ser Uncertain significance ★★ ⚠ 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

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-pro475 (accessed [today's date]).

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