MET p.Ser548=
c.1644G>A · rs750584257 · VCV216501
Benign/Likely benign
Multiple submitters
Classification
Benign/Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 5 submitters
gnomAD v4.1
Rare
very rare (popmax 0.005%, amr)
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 -1.2 | GERP -3.8 |
| Overall | ||
| CADD | 2.785 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.005%
Admixed American · 3/60,006 alleles
Filtering AF
0.00133%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.000668%
Overall
0.000558%
9/1,614,016 alleles · very rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Admixed Americangrpmax | 0.005% | 20,002 |
| African / African-American | 0.00267% | 37,500 |
| South Asian | 0.0022% | 45,531 |
| European (non-Finnish) | 0.000169% | 590,005 |
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.Ser548=
- Coding
- c.1644G>A
- MANE Select
- NM_024755 · reported on NM_000245
- dbSNP
- rs750584257
- Type
- single nucleotide variant
- Location
- chr7:116740968 (GRCh38)
- Structure
- AlphaFold pLDDT 52.38
- Residue 548
- the 'disordered' region
Similar variants
- MET p.Ser548Leu Conflicting classifications of pathogenicity ★ ⚠ same residue
- MET p.Ser548Trp Conflicting classifications of pathogenicity ★ ⚠ 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
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-ser548 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown