Is MET p.Lys40= (c.120G>A) pathogenic?

MET p.Lys40= (c.120G>A) is classified Benign in MET (ClinVar, Single submitter, 1 submitter; last evaluated 2024-11-06). Very rare (popmax 0.00167%, amr); Associated with Papillary renal cell carcinoma type 1.

What condition is associated with MET p.Lys40= (c.120G>A)?

MET p.Lys40= (c.120G>A) is associated with Papillary renal cell carcinoma type 1 (ClinVar).

How common is MET p.Lys40= (c.120G>A) in the general population?

MET p.Lys40= (c.120G>A) is very rare (popmax 0.00167%, amr) (gnomAD).

MET p.Lys40=

c.120G>A · VCV3773405

Benign Single submitter

Classification

Benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00167%, amr)

Conditions

Papillary renal cell carcinoma type 1

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 0.076	GERP -0.11, phastCons 0.57
Overall
CADD	4.521	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00167% Admixed American · 1/59,984 alleles

Overall 0.000137% 2/1,461,696 alleles · very rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00167%	59,984
European (non-Finnish)	8.48e-05%	1,179,906

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.Lys40=
Coding: c.120G>A
MANE Select: NM_000245
Type: single nucleotide variant
Location: chr7:116699204 (GRCh38)
Gene constraint: LOEUF 0.446 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 79.28 · 130 PDB
Residue 40: the sema domain

Full MET gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Papillary renal cell carcinoma type 1 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

MET p.Lys40Met Conflicting classifications of pathogenicity ★ ⚠ same residue
MET c.-64G>T Uncertain significance ★★ same condition
MET p.Ala973Thr Uncertain significance ★★ ⚠ same condition
MET p.Glu1082Asp Uncertain significance ★★ ⚠ same condition
MET p.Ser283Pro Uncertain significance ★★ ⚠ same condition
MET c.1201-13T>C Likely benign ★★ same condition
MET c.1528-9T>C Likely benign ★★ same condition
MET c.1702-11T>C Likely benign ★★ 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-lys40 (accessed [today's date]).

Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown