Is MET p.Ser1390= (c.4170A>T) pathogenic?

MET p.Ser1390= (c.4170A>T) is classified Likely benign in MET (ClinVar, Single submitter, 1 submitter; last evaluated 2020-09-10). Very rare (popmax 0.00439%, sas); Associated with hereditary neoplastic syndrome.

What condition is associated with MET p.Ser1390= (c.4170A>T)?

MET p.Ser1390= (c.4170A>T) is associated with hereditary neoplastic syndrome (ClinVar).

How common is MET p.Ser1390= (c.4170A>T) in the general population?

MET p.Ser1390= (c.4170A>T) is very rare (popmax 0.00439%, sas) (gnomAD).

MET p.Ser1390=

c.4170A>T · rs1584978746 · VCV1738847

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00439%, 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 -0.44	GERP -3
Overall
CADD	0.868	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00439% South Asian · 4/91,078 alleles

Filtering AF 0.00143% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000891%

Overall 0.000248% 4/1,613,620 alleles · very rare exomes 4/1,461,290 · genomes 0/152,330 · 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.Ser1390=
Coding: c.4170A>T
MANE Select: NM_000245
dbSNP: rs1584978746
Type: single nucleotide variant
Location: chr7:116796121 (GRCh38)
Gene constraint: LOEUF 0.446 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 79.28 · 130 PDB
Residue 1390: the 'interaction with ranbp9' region

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.Ser1390Leu 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
MET c.1392+3A>G 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-ser1390 (accessed [today's date]).

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