MET p.Leu238=
c.714A>G · rs2116596040 · VCV3233007
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
very rare (popmax 0.00167%, 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 0.3 | GERP -3.7, phastCons 0.41 |
| Overall | ||
| CADD | 2.208 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00167%
Admixed American · 1/60,020 alleles
Overall
6.84e-05%
1/1,461,796 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.Leu238=
- Coding
- c.714A>G
- MANE Select
- NM_024755 · reported on NM_000245
- dbSNP
- rs2116596040
- Type
- single nucleotide variant
- Location
- chr7:116699798 (GRCh38)
- Structure
- AlphaFold pLDDT 52.38
- Residue 238
- the 'disordered' region
Similar variants
- MET p.Leu238Ser 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
- MET c.1392+3A>G 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-leu238 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown