Is MET p.Ala119Val (c.356C>T) pathogenic?

MET p.Ala119Val (c.356C>T) is classified Uncertain significance in MET (ClinVar, Multiple submitters, 4 submitters; last evaluated 2025-07-23). AlphaMissense: likely benign (0.1773); Very rare (popmax 0.00167%, amr); Associated with renal cell carcinoma.

What condition is associated with MET p.Ala119Val (c.356C>T)?

MET p.Ala119Val (c.356C>T) is associated with renal cell carcinoma, autosomal recessive nonsyndromic hearing loss 97, hereditary neoplastic syndrome (ClinVar).

How common is MET p.Ala119Val (c.356C>T) in the general population?

MET p.Ala119Val (c.356C>T) is very rare (popmax 0.00167%, amr) (gnomAD).

What do computational predictors say about MET p.Ala119Val (c.356C>T)?

AlphaMissense predicts likely benign (score 0.1773) — an in-silico prediction, not a clinical call.

MET p.Ala119Val

c.356C>T · rs904162290 · VCV454242

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

AlphaMissense

likely benign

0.1773 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00167%, amr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

renal cell carcinoma

Computational evidence

Protein change
AlphaMissense	0.1773	likely benign
REVEL	0.245	benign-leaning
SaProt	LLR -5.89	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 4.1	GERP 0.87, phastCons 1
Overall
CADD	22.1	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00167% Admixed American · 1/59,988 alleles

Filtering AF 0.000429% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000312%

Overall 0.000682% 11/1,613,932 alleles · very rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00167%	59,988
European (non-Finnish)	0.000847%	117,995

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.Ala119Val
Coding: c.356C>T
MANE Select: NM_024755 · reported on NM_000245
dbSNP: rs904162290
Type: single nucleotide variant
Location: chr7:116699440 (GRCh38)
Structure: AlphaFold pLDDT 52.38
Residue 119: the 'disordered' 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: autosomal recessive nonsyndromic hearing loss 97 hereditary neoplastic syndrome

Similar variants

MET p.Ala119Ser Uncertain significance ★ ⚠ same residue
MET p.Ala119Asp 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
MET c.1392+1G>T 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-ala119val (accessed [today's date]).

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