Is MET p.Ile316Met (c.948A>G) pathogenic?

MET p.Ile316Met (c.948A>G) is classified Benign/Likely benign in MET (ClinVar, Multiple submitters, 21 submitters; last evaluated 2026-02-03). AlphaMissense: likely benign (0.1934); Low-frequency (popmax 2.05%, afr); Associated with renal cell carcinoma.

What condition is associated with MET p.Ile316Met (c.948A>G)?

MET p.Ile316Met (c.948A>G) is associated with renal cell carcinoma, hepatocellular carcinoma, osteofibrous dysplasia (ClinVar).

How common is MET p.Ile316Met (c.948A>G) in the general population?

MET p.Ile316Met (c.948A>G) is low-frequency (popmax 2.05%, afr) (gnomAD).

What do computational predictors say about MET p.Ile316Met (c.948A>G)?

AlphaMissense predicts likely benign (score 0.1934) — an in-silico prediction, not a clinical call.

MET p.Ile316Met

c.948A>G · rs35225896 · VCV41629

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 21 submitters

AlphaMissense

likely benign

0.1934 · ACMG-weighted

gnomAD v4.1

Rare

low-frequency (popmax 2.05%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

renal cell carcinoma

Computational evidence

Protein change
AlphaMissense	0.1934	likely benign
REVEL	0.185	benign-leaning
SaProt	LLR -9.18	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 -0.16	GERP -3.7, phastCons 0.57
Overall
CADD	17.34	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 2.05% African / African-American · 1,540/75,032 alleles

Filtering AF 1.97% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.93%

Overall 0.135% 2,179/1,614,038 alleles · low-frequency

Ancestry group	Frequency	1 in
African / African-Americangrpmax	2.05%	49
Admixed American	0.215%	465
Remaining individualsnot grpmax-eligible	0.206%	485
Ashkenazi Jewishnot grpmax-eligible	0.186%	538
Middle Eastern	0.099%	1,010
European (non-Finnish)	0.027%	3,699
South Asian	0.0011%	91,076

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.Ile316Met
Coding: c.948A>G
MANE Select: NM_000245
dbSNP: rs35225896
Type: single nucleotide variant
Location: chr7:116700032 (GRCh38)
Gene constraint: LOEUF 0.446 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 79.28 · 130 PDB
Residue 316: a β-strand; a disulfide bond; the sema domain; a UniProt-annotated variant site (in)

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: hepatocellular carcinoma osteofibrous dysplasia autosomal recessive nonsyndromic hearing loss 97 hereditary neoplastic syndrome arthrogryposis, distal, IIa 11

Similar variants

MET p.Ile316= Likely benign ★★ same residue
MET p.Ile316Thr Uncertain significance ★ ⚠ same residue
MET p.Ile316Val 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
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-ile316met (accessed [today's date]).

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