MET p.Ile377=
c.1131C>A · rs28444388 · VCV485769
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
very rare (popmax 0.00182%, 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 -7.8 | GERP -3.7 |
| Overall | ||
| CADD | 0.13 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00182%
Admixed American · 1/55,040 alleles
Filtering AF
2.8e-05%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 1.1e-05%
Overall
0.000188%
3/1,594,280 alleles · very rare
exomes 2/1,442,190 · genomes 1/152,090 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Admixed Americangrpmax | 0.00182% | 55,040 |
| European (non-Finnish) | 0.00017% | 587,072 |
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.Ile377=
- Coding
- c.1131C>A
- MANE Select
- NM_000245
- dbSNP
- rs28444388
- Type
- single nucleotide variant
- Location
- chr7:116700215 (GRCh38)
- Gene constraint
- LOEUF 0.446 · pLI 1.00 (gnomAD)
- Structure
- AlphaFold pLDDT 79.28 · 130 PDB
- Residue 377
- the sema domain
Similar variants
- MET p.Ile377Ser Uncertain significance ★★ ⚠ same residue
- MET p.Ile377Met Uncertain significance ★ ⚠ same residue
- MET p.Ile377Thr Uncertain significance ★ ⚠ same residue
- MET p.Ile377Val 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
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-ile377 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown