Is MET p.Asp1373= (c.4119T>C) pathogenic?

MET p.Asp1373= (c.4119T>C) is classified Likely benign in MET (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-10-02). Very rare (popmax 0.00223%, eas); Associated with renal cell carcinoma.

What condition is associated with MET p.Asp1373= (c.4119T>C)?

MET p.Asp1373= (c.4119T>C) is associated with renal cell carcinoma, hereditary neoplastic syndrome (ClinVar).

How common is MET p.Asp1373= (c.4119T>C) in the general population?

MET p.Asp1373= (c.4119T>C) is very rare (popmax 0.00223%, eas) (gnomAD).

MET p.Asp1373=

c.4119T>C · rs771571698 · VCV1149846

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

very rare (popmax 0.00223%, eas)

Conditions

renal cell carcinoma

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 -0.54	GERP -3.6
Overall
CADD	0.883	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00223% East Asian · 1/44,870 alleles

Overall 0.000137% 2/1,461,716 alleles · very rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00223%	44,870
European (non-Finnish)	8.48e-05%	1,179,917

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.Asp1373=
Coding: c.4119T>C
MANE Select: NM_000245
dbSNP: rs771571698
Type: single nucleotide variant
Location: chr7:116796070 (GRCh38)
Gene constraint: LOEUF 0.446 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 79.28 · 130 PDB
Residue 1373: the 'interaction with ranbp9' region

Full MET gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

renal cell carcinoma — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: hereditary neoplastic syndrome

Similar variants

MET p.Asp1373Gly Conflicting classifications of pathogenicity ★ ⚠ same residue
MET p.Asp1373His Conflicting classifications of pathogenicity ★ ⚠ same residue
MET p.Asp1373Tyr Uncertain significance ★ ⚠ same residue
MET p.Asp1373Val Conflicting classifications of pathogenicity ★ ⚠ 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

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-asp1373 (accessed [today's date]).

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