Is MET p.Val383= (c.1149G>A) pathogenic?

MET p.Val383= (c.1149G>A) is classified Conflicting classifications of pathogenicity in MET (ClinVar, Conflicting submitters, 3 submitters; last evaluated 2025-07-07). Very rare (popmax 0.00114%, sas); Associated with hereditary neoplastic syndrome.

What condition is associated with MET p.Val383= (c.1149G>A)?

MET p.Val383= (c.1149G>A) is associated with hereditary neoplastic syndrome, renal cell carcinoma (ClinVar).

How common is MET p.Val383= (c.1149G>A) in the general population?

MET p.Val383= (c.1149G>A) is very rare (popmax 0.00114%, sas) (gnomAD).

MET p.Val383=

c.1149G>A · rs1033586067 · VCV1623143

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 3 submitters

gnomAD v4.1

Rare

very rare (popmax 0.00114%, sas)

Conditions

hereditary neoplastic syndrome

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 3	GERP -0.028, phastCons 1
Overall
CADD	14.5	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00114% South Asian · 1/87,802 alleles

Overall 6.24e-05% 1/1,601,460 alleles · very rare exomes 1/1,449,146 · genomes 0/152,314 · joint denominator

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.Val383=
Coding: c.1149G>A
MANE Select: NM_000245
dbSNP: rs1033586067
Type: single nucleotide variant
Location: chr7:116700233 (GRCh38)
Gene constraint: LOEUF 0.446 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 79.28 · 130 PDB
Residue 383: a β-strand; the sema 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

Also linked: renal cell carcinoma

Similar variants

MET p.Val383Gly Uncertain significance ★ ⚠ same residue
MET p.Val383Met 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
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-val383 (accessed [today's date]).

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