Is MET p.Ser1338= (c.4014A>G) pathogenic?

MET p.Ser1338= (c.4014A>G) is classified Likely benign in MET (ClinVar, Single submitter, 1 submitter; last evaluated 2019-08-31). Absent from gnomAD v4.1; Associated with hereditary neoplastic syndrome.

What condition is associated with MET p.Ser1338= (c.4014A>G)?

MET p.Ser1338= (c.4014A>G) is associated with hereditary neoplastic syndrome (ClinVar).

How common is MET p.Ser1338= (c.4014A>G) in the general population?

MET p.Ser1338= (c.4014A>G) is absent from gnomAD v4.1 (gnomAD).

MET p.Ser1338=

c.4014A>G · rs2117111594 · VCV1737512

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Absent

absent from gnomAD v4.1

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 -2.1	GERP -3.6
Overall
CADD	0.492	PHRED · no single calibrated threshold — expert panels disagree

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.Ser1338=
Coding: c.4014A>G
MANE Select: NM_000245
dbSNP: rs2117111594
Type: single nucleotide variant
Location: chr7:116795965 (GRCh38)
Gene constraint: LOEUF 0.446 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 79.28 · 130 PDB
Residue 1338: the 'interaction with ranbp9' region; the 'interaction with muc20' region; an α-helix; the protein kinase 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.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
MET c.1392+5G>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-ser1338 (accessed [today's date]).

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