Is MET p.Ile367Val (c.1099A>G) pathogenic?

MET p.Ile367Val (c.1099A>G) is classified Conflicting classifications of pathogenicity in MET (ClinVar, Conflicting submitters, 6 submitters; last evaluated 2025-12-23). AlphaMissense: likely benign (0.0639); Very rare (popmax 0.00222%, nfe); Associated with Papillary renal cell carcinoma type 1.

What condition is associated with MET p.Ile367Val (c.1099A>G)?

MET p.Ile367Val (c.1099A>G) is associated with Papillary renal cell carcinoma type 1, renal cell carcinoma, hereditary neoplastic syndrome (ClinVar).

How common is MET p.Ile367Val (c.1099A>G) in the general population?

MET p.Ile367Val (c.1099A>G) is very rare (popmax 0.00222%, nfe) (gnomAD).

What do computational predictors say about MET p.Ile367Val (c.1099A>G)?

AlphaMissense predicts likely benign (score 0.0639) — an in-silico prediction, not a clinical call.

MET p.Ile367Val

c.1099A>G · rs774146015 · VCV480850

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 6 submitters

AlphaMissense

likely benign

0.0639 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00222%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Papillary renal cell carcinoma type 1

Computational evidence

Protein change
AlphaMissense	0.0639	likely benign
REVEL	0.033	moderately benign-leaning
SaProt	LLR -6.68	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 3.5	GERP -3, phastCons 0.99
Overall
CADD	5.206	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00222% European (non-Finnish) · 26/1,172,216 alleles

Filtering AF 0.00154% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00131%

Overall 0.00176% 28/1,593,180 alleles · very rare exomes 27/1,440,988 · genomes 1/152,192 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00222%	45,085
Remaining individualsnot grpmax-eligible	0.00162%	61,604
African / African-American	0.00135%	73,934

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.Ile367Val
Coding: c.1099A>G
MANE Select: NM_000245
dbSNP: rs774146015
Type: single nucleotide variant
Location: chr7:116700183 (GRCh38)
Gene constraint: LOEUF 0.446 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 79.28 · 130 PDB
Residue 367: an α-helix; the sema domain

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

Disease context

Papillary renal cell carcinoma type 1 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: renal cell carcinoma hereditary neoplastic syndrome

Similar variants

MET p.Ile367Asn Uncertain significance ★★ ⚠ same residue
MET p.Ile367Thr Uncertain significance ★ ⚠ same residue
MET p.Ile367= 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

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-ile367val (accessed [today's date]).

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