Is MET p.Pro210Ser (c.628C>T) pathogenic?

MET p.Pro210Ser (c.628C>T) is classified Conflicting classifications of pathogenicity in MET (ClinVar, Conflicting submitters, 2 submitters; last evaluated 2025-12-12). AlphaMissense: likely benign (0.0635); Very rare (popmax 0.000169%, nfe); Associated with renal cell carcinoma.

What condition is associated with MET p.Pro210Ser (c.628C>T)?

MET p.Pro210Ser (c.628C>T) is associated with renal cell carcinoma, hereditary neoplastic syndrome (ClinVar).

How common is MET p.Pro210Ser (c.628C>T) in the general population?

MET p.Pro210Ser (c.628C>T) is very rare (popmax 0.000169%, nfe) (gnomAD).

What do computational predictors say about MET p.Pro210Ser (c.628C>T)?

AlphaMissense predicts likely benign (score 0.0635) — an in-silico prediction, not a clinical call.

MET p.Pro210Ser

c.628C>T · rs983457211 · VCV845103

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.0635 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000169%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

renal cell carcinoma

Computational evidence

Protein change
AlphaMissense	0.0635	likely benign
REVEL	0.035	moderately benign-leaning
SaProt	LLR -3.78	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 2.4	GERP -2.5, phastCons 0.99
Overall
CADD	0.305	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 0.000169% European (non-Finnish) · 2/1,179,958 alleles

Filtering AF 2.8e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.1e-05%

Overall 0.000137% 2/1,461,782 alleles · very rare

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.Pro210Ser
Coding: c.628C>T
MANE Select: NM_000245
dbSNP: rs983457211
Type: single nucleotide variant
Location: chr7:116699712 (GRCh38)
Gene constraint: LOEUF 0.446 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 79.28 · 130 PDB
Residue 210: the sema domain

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.Pro210= Benign/Likely benign ★★ same residue
MET p.Pro210Thr Conflicting classifications of pathogenicity ★ ⚠ same residue
MET p.Pro210Leu Likely benign ★ same residue
MET p.Pro210fs 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

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-pro210ser (accessed [today's date]).

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