MET p.Pro356=
c.1068A>G · rs934426317 · VCV454176
Benign/Likely benign
Multiple submitters
Classification
Benign/Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 3 submitters
gnomAD v4.1
Rare
very rare (popmax 0.00111%, nfe)
Conditions
2
renal cell carcinoma
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 -2.9 | GERP -3.7 |
| Overall | ||
| CADD | 0.461 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00111%
European (non-Finnish) · 13/1,171,800 alleles
Filtering AF
0.000619%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.000477%
Overall
0.000815%
13/1,595,852 alleles · very rare
Rarity supports pathogenicity (ACMG PM2); frequency above a disease-specific BA1/BS1 threshold argues against it. A variant frequent in one ancestry group can be near-absent in others, so a single global figure can mislead.
Variant & gene context
- Gene
- MET
- Protein
- p.Pro356=
- Coding
- c.1068A>G
- MANE Select
- NM_024755 · reported on NM_000245
- dbSNP
- rs934426317
- Type
- single nucleotide variant
- Location
- chr7:116700152 (GRCh38)
- Structure
- AlphaFold pLDDT 52.38
- Residue 356
- the 'disordered' region
Similar variants
- MET p.Pro356Leu Uncertain significance ★★ ⚠ same residue
- MET p.Pro356Thr Uncertain significance ★★ ⚠ same residue
- MET p.Pro356Ser Uncertain significance ★ ⚠ same residue
- MET p.Pro356fs 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
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-pro356 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown