Is MET p.Gln348= (c.1044A>G) pathogenic?

MET p.Gln348= (c.1044A>G) is classified Benign/Likely benign in MET (ClinVar, Multiple submitters, 2 submitters; last evaluated 2024-11-07). Very rare (popmax 0.00223%, eas); Associated with hereditary neoplastic syndrome.

What condition is associated with MET p.Gln348= (c.1044A>G)?

MET p.Gln348= (c.1044A>G) is associated with hereditary neoplastic syndrome (ClinVar).

How common is MET p.Gln348= (c.1044A>G) in the general population?

MET p.Gln348= (c.1044A>G) is very rare (popmax 0.00223%, eas) (gnomAD).

MET p.Gln348=

c.1044A>G · rs1266319879 · VCV1774896

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

very rare (popmax 0.00223%, eas)

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
Pangolin	Δ0.31	gain · loss 0.00 · not in the SpliceAI release · independent
Constraint at this position
Conservation	phyloP 0.65	GERP -3.7, phastCons 0.92
Overall
CADD	2.774	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00223% East Asian · 1/44,784 alleles

Overall 0.000125% 2/1,603,038 alleles · very rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00223%	44,784
European (non-Finnish)	8.51e-05%	1,174,876

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.Gln348=
Coding: c.1044A>G
MANE Select: NM_000245
dbSNP: rs1266319879
Type: single nucleotide variant
Location: chr7:116700128 (GRCh38)
Gene constraint: LOEUF 0.446 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 79.28 · 130 PDB
Residue 348: a β-strand; a disulfide bond; 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

Similar variants

MET p.Gln348Leu Uncertain significance ★★ ⚠ same residue
MET p.Gln348Lys Uncertain significance ★★ ⚠ same residue
MET p.Gln348Ter Uncertain significance ★ 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

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-gln348 (accessed [today's date]).

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