Is MET p.Ser178= (c.534C>T) pathogenic?

MET p.Ser178= (c.534C>T) is classified Benign in MET (ClinVar, Multiple submitters, 18 submitters; last evaluated 2026-02-04). Common (popmax 14%, afr) — too common for a highly-penetrant pathogenic allele; Associated with renal cell carcinoma.

What condition is associated with MET p.Ser178= (c.534C>T)?

MET p.Ser178= (c.534C>T) is associated with renal cell carcinoma, autosomal recessive nonsyndromic hearing loss 97, hereditary neoplastic syndrome (ClinVar).

MET p.Ser178=

Q: How common is MET p.Ser178= (c.534C>T) in the general population?

MET p.Ser178= (c.534C>T) is common (popmax 14%, afr) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.534C>T · rs35775721 · VCV93578

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 18 submitters

gnomAD v4.1

Common

common (popmax 14%, afr) — too common for a highly-penetrant pathogenic allele

Conditions

renal cell carcinoma

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Pangolin	Δ0.33	gain · loss 0.00 · not in the SpliceAI release · independent
Constraint at this position
Conservation	phyloP -2.4	GERP -3.7
Overall
CADD	6.436	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 14% African / African-American · 10,519/74,964 alleles

Filtering AF 13.8% ClinGen BA1/BS1 input FAF95, joint · FAF99 13.7%

Overall 4.82% 77,825/1,613,868 alleles · common

Ancestry group	Frequency	1 in
African / African-Americangrpmax	14%	7
South Asian	11.3%	9
Middle Eastern	9.11%	11
Remaining individualsnot grpmax-eligible	5.51%	18
Amishnot grpmax-eligible	5.48%	18
East Asian	5.24%	19
Finnishnot grpmax-eligible	5.04%	20
European (non-Finnish)	3.77%	27
Ashkenazi Jewishnot grpmax-eligible	3.42%	29
Admixed American	3.14%	32

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.Ser178=
Coding: c.534C>T
MANE Select: NM_024755 · reported on NM_000245
dbSNP: rs35775721
Type: single nucleotide variant
Location: chr7:116699618 (GRCh38)
Structure: AlphaFold pLDDT 52.38
Residue 178: 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.Ser178Gly Uncertain significance ★★ ⚠ same residue
MET p.Ser178Asn 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-ser178 (accessed [today's date]).

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