Is MET p.Val892Ala (c.2675T>C) pathogenic?

MET p.Val892Ala (c.2675T>C) is classified Uncertain significance in MET (ClinVar, Single submitter, 1 submitter; last evaluated 2025-10-28). AlphaMissense: likely benign (0.3016); Absent from gnomAD v4.1; Associated with hereditary neoplastic syndrome.

What condition is associated with MET p.Val892Ala (c.2675T>C)?

MET p.Val892Ala (c.2675T>C) is associated with hereditary neoplastic syndrome (ClinVar).

How common is MET p.Val892Ala (c.2675T>C) in the general population?

MET p.Val892Ala (c.2675T>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about MET p.Val892Ala (c.2675T>C)?

AlphaMissense predicts likely benign (score 0.3016) — an in-silico prediction, not a clinical call.

MET p.Val892Ala

c.2675T>C · VCV4648425

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.3016 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

hereditary neoplastic syndrome

Computational evidence

Protein change
AlphaMissense	0.3016	likely benign
REVEL	0.396	indeterminate
SaProt	LLR -11.37	damaging
⇒ SaProt calls this damaging; AlphaMissense does not; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.9	GERP 1.8, phastCons 1
Overall
CADD	23.3	PHRED · no single calibrated threshold — expert panels disagree

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.Val892Ala
Coding: c.2675T>C
MANE Select: NM_000245
Type: single nucleotide variant
Location: chr7:116769736 (GRCh38)
Gene constraint: LOEUF 0.446 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 79.28 · 130 PDB

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.Val892Ile Conflicting classifications of pathogenicity ★ ⚠ same residue
MET p.Val892= 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
MET c.1200+2T>C Uncertain significance ★★ same condition
MET c.1392+1G>T Uncertain significance ★★ 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-val892ala (accessed [today's date]).

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