Is MET p.Ser617Arg (c.1851C>G) pathogenic?

MET p.Ser617Arg (c.1851C>G) is classified Uncertain significance in MET (ClinVar, Single submitter, 1 submitter; last evaluated 2025-05-15). AlphaMissense: likely pathogenic (0.9105); Absent from gnomAD v4.1; Associated with hereditary neoplastic syndrome.

What condition is associated with MET p.Ser617Arg (c.1851C>G)?

MET p.Ser617Arg (c.1851C>G) is associated with hereditary neoplastic syndrome (ClinVar).

How common is MET p.Ser617Arg (c.1851C>G) in the general population?

MET p.Ser617Arg (c.1851C>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about MET p.Ser617Arg (c.1851C>G)?

AlphaMissense predicts likely pathogenic (score 0.9105) — an in-silico prediction, not a clinical call.

MET p.Ser617Arg

c.1851C>G · VCV4053972

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9105 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

hereditary neoplastic syndrome

Computational evidence

Protein change
AlphaMissense	0.9105	likely pathogenic
REVEL	0.778	moderately pathogenic-leaning
SaProt	LLR -13.73	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 1.4	GERP -0.34, phastCons 1
Overall
CADD	22.0	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — 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.Ser617Arg
Coding: c.1851C>G
MANE Select: NM_000245
Type: single nucleotide variant
Location: chr7:116755504 (GRCh38)
Gene constraint: LOEUF 0.446 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 79.28 · 130 PDB
Residue 617: the ipt/tig 1 domain

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

Disease context

hereditary neoplastic syndrome — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

MET p.Ser617Asn Uncertain significance ★★ ⚠ same residue
MET p.Ser617Cys Uncertain significance ★ ⚠ same residue
MET p.Ser617Gly Uncertain significance ★ ⚠ same residue
MET p.Ser617= 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-ser617arg (accessed [today's date]).

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