MET p.Ala320=
c.960G>A · rs191198682 · VCV135979
Benign/Likely benign
Multiple submitters
Classification
Benign/Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 6 submitters
gnomAD v4.1
Rare
ultra-rare (popmax 0.0156%, eas)
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 -8.8 | GERP -3.7 |
| Overall | ||
| CADD | 0.115 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0156%
East Asian · 7/44,886 alleles
Filtering AF
0.00726%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00514%
Overall
0.00266%
43/1,613,932 alleles · ultra-rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| East Asiangrpmax | 0.0156% | 6,412 |
| African / African-American | 0.012% | 8,334 |
| South Asian | 0.00549% | 18,210 |
| European (non-Finnish) | 0.00178% | 56,188 |
| Admixed American | 0.00167% | 59,966 |
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.Ala320=
- Coding
- c.960G>A
- MANE Select
- NM_000245
- dbSNP
- rs191198682
- Type
- single nucleotide variant
- Location
- chr7:116700044 (GRCh38)
- Gene constraint
- LOEUF 0.446 · pLI 1.00 (gnomAD)
- Structure
- AlphaFold pLDDT 79.28 · 130 PDB
- Residue 320
- a β-strand; a disulfide bond; the sema domain; a UniProt-annotated variant site (in)
Similar variants
- MET p.Ala320Thr Uncertain significance ★ ⚠ same residue
- MET p.Ala320Val 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-ala320 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown