Is MET p.Arg970His (c.2909G>A) pathogenic?

MET p.Arg970His (c.2909G>A) is classified Conflicting classifications of pathogenicity in MET (ClinVar, Conflicting submitters, 7 submitters; last evaluated 2026-01-25). AlphaMissense: likely benign (0.0827); Very rare (popmax 0.00534%, afr); Associated with renal cell carcinoma.

What condition is associated with MET p.Arg970His (c.2909G>A)?

MET p.Arg970His (c.2909G>A) is associated with renal cell carcinoma, autosomal recessive nonsyndromic hearing loss 97, hereditary neoplastic syndrome (ClinVar).

How common is MET p.Arg970His (c.2909G>A) in the general population?

MET p.Arg970His (c.2909G>A) is very rare (popmax 0.00534%, afr) (gnomAD).

What do computational predictors say about MET p.Arg970His (c.2909G>A)?

AlphaMissense predicts likely benign (score 0.0827) — an in-silico prediction, not a clinical call.

MET p.Arg970His

c.2909G>A · rs45607832 · VCV188184

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 7 submitters

AlphaMissense

likely benign

0.0827 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00534%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

renal cell carcinoma

Computational evidence

Protein change
AlphaMissense	0.0827	likely benign
REVEL	0.263	benign-leaning
SaProt	LLR -6.09	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 10	GERP 1.9, phastCons 1
Overall
CADD	25.8	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 0.00534% African / African-American · 4/74,858 alleles

Filtering AF 0.00175% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00104%

Overall 0.00155% 25/1,613,616 alleles · very rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00534%	18,715
Admixed American	0.00334%	29,978
Remaining individualsnot grpmax-eligible	0.0032%	31,235
East Asian	0.00223%	44,856
South Asian	0.0022%	45,534
European (non-Finnish)	0.00119%	84,274

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.Arg970His
Coding: c.2909G>A
MANE Select: NM_000245
dbSNP: rs45607832
Type: single nucleotide variant
Location: chr7:116771870 (GRCh38)
Gene constraint: LOEUF 0.446 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 79.28 · 130 PDB
Residue 970: a UniProt-annotated variant site (in osfd; loss of cbl-mediated destabilization); 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: autosomal recessive nonsyndromic hearing loss 97 hereditary neoplastic syndrome

Similar variants

MET p.Arg970Cys Conflicting classifications of pathogenicity ★ ⚠ same residue
MET p.Arg970Leu Uncertain significance ★ ⚠ same residue
MET p.Arg970Pro Uncertain significance ★ same residue
MET p.Arg970= 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

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-arg970his (accessed [today's date]).

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