MET p.Ser1056=
c.3168T>C · rs376069508 · VCV132742
Benign/Likely benign
Multiple submitters
Classification
Benign/Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 8 submitters
gnomAD v4.1
Rare
ultra-rare (popmax 0.0138%, 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 -2.5 | GERP -3.8 |
| Overall | ||
| CADD | 1.925 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0138%
European (non-Finnish) · 163/1,180,034 alleles
Filtering AF
0.0121%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0114%
Overall
0.0105%
170/1,614,116 alleles · ultra-rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| European (non-Finnish)grpmax | 0.0138% | 7,239 |
| Remaining individualsnot grpmax-eligible | 0.0064% | 15,621 |
| African / African-American | 0.004% | 24,983 |
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.Ser1056=
- Coding
- c.3168T>C
- MANE Select
- NM_000245
- dbSNP
- rs376069508
- Type
- single nucleotide variant
- Location
- chr7:116775020 (GRCh38)
- Gene constraint
- LOEUF 0.446 · pLI 1.00 (gnomAD)
- Structure
- AlphaFold pLDDT 79.28 · 130 PDB
- Residue 1056
- an α-helix
Similar variants
- MET p.Ser1056Asn Uncertain significance ★★ ⚠ same residue
- MET p.Ser1056Arg Uncertain significance ★ ⚠ same residue
- MET p.Ser1056Gly 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-ser1056 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown