Is MET p.Lys751Gln (c.2251A>C) pathogenic?

MET p.Lys751Gln (c.2251A>C) is classified Uncertain significance in MET (ClinVar, Single submitter, 1 submitter; last evaluated 2024-05-18). AlphaMissense: likely benign (0.1658); Absent from gnomAD v4.1; Associated with renal cell carcinoma.

What condition is associated with MET p.Lys751Gln (c.2251A>C)?

MET p.Lys751Gln (c.2251A>C) is associated with renal cell carcinoma (ClinVar).

How common is MET p.Lys751Gln (c.2251A>C) in the general population?

MET p.Lys751Gln (c.2251A>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about MET p.Lys751Gln (c.2251A>C)?

AlphaMissense predicts likely benign (score 0.1658) — an in-silico prediction, not a clinical call.

MET p.Lys751Gln

c.2251A>C · VCV3653757

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1658 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

renal cell carcinoma

Computational evidence

Protein change
AlphaMissense	0.1658	likely benign
REVEL	0.426	indeterminate
SaProt	LLR -8.96	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 11	GERP 1.9, phastCons 1
Overall
CADD	23.7	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: MET
Protein: p.Lys751Gln
Coding: c.2251A>C
MANE Select: NM_000245
Type: single nucleotide variant
Location: chr7:116758607 (GRCh38)
Gene constraint: LOEUF 0.446 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 79.28 · 130 PDB
Residue 751: the ipt/tig 3 domain

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

Disease context

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

Similar variants

MET p.Lys751= Likely benign ★★ same residue
MET p.Lys751Arg Uncertain significance ★ ⚠ same residue
MET p.Lys751Asn Uncertain significance ★ ⚠ same residue
MET p.Lys751Glu Uncertain significance ★ ⚠ 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-lys751gln (accessed [today's date]).

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