Is MET p.His150Pro (c.449A>C) pathogenic?

MET p.His150Pro (c.449A>C) is classified Uncertain significance in MET (ClinVar, Single submitter, 1 submitter; last evaluated 2024-02-15). AlphaMissense: likely benign (0.1185); Very rare (popmax 0.00223%, eas); Associated with renal cell carcinoma.

What condition is associated with MET p.His150Pro (c.449A>C)?

MET p.His150Pro (c.449A>C) is associated with renal cell carcinoma (ClinVar).

How common is MET p.His150Pro (c.449A>C) in the general population?

MET p.His150Pro (c.449A>C) is very rare (popmax 0.00223%, eas) (gnomAD).

What do computational predictors say about MET p.His150Pro (c.449A>C)?

AlphaMissense predicts likely benign (score 0.1185) — an in-silico prediction, not a clinical call.

MET p.His150Pro

c.449A>C · VCV3701715

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1185 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00223%, eas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

renal cell carcinoma

Computational evidence

Protein change
AlphaMissense	0.1185	likely benign
REVEL	0.233	benign-leaning
SaProt	LLR -9.69	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 6.9	GERP 1.9, phastCons 0.89
Overall
CADD	10.89	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

Grpmax group 0.00223% East Asian · 1/44,880 alleles

Overall 6.84e-05% 1/1,461,762 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.His150Pro
Coding: c.449A>C
MANE Select: NM_000245
Type: single nucleotide variant
Location: chr7:116699533 (GRCh38)
Gene constraint: LOEUF 0.446 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 79.28 · 130 PDB
Residue 150: a disulfide bond; the sema domain; a UniProt-annotated variant site (found in a case of cancer of unknown primary origin; uncertain significance; somatic mutation)

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.His150= Likely benign ★★ same residue
MET p.His150Tyr Conflicting classifications of pathogenicity ★ ⚠ same residue
MET p.His150Arg Likely benign ★ same residue
MET p.His150Gln Likely benign ★ 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-his150pro (accessed [today's date]).

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