Is SMARCB1 p.Arg366= (c.1098C>T) pathogenic?

SMARCB1 p.Arg366= (c.1098C>T) is classified Benign/Likely benign in SMARCB1 (ClinVar, Multiple submitters, 5 submitters; last evaluated 2026-01-31). Rare (popmax 0.125%, sas); Associated with hereditary neoplastic syndrome.

What condition is associated with SMARCB1 p.Arg366= (c.1098C>T)?

SMARCB1 p.Arg366= (c.1098C>T) is associated with hereditary neoplastic syndrome (ClinVar).

How common is SMARCB1 p.Arg366= (c.1098C>T) in the general population?

SMARCB1 p.Arg366= (c.1098C>T) is rare (popmax 0.125%, sas) (gnomAD).

SMARCB1 p.Arg366=

c.1098C>T · rs562018506 · VCV703275

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 5 submitters

gnomAD v4.1

Rare

rare (popmax 0.125%, sas)

Conditions

hereditary neoplastic syndrome

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
Constraint at this position
Conservation	phyloP -7.1	GERP -2.5
Overall
CADD	1.064	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.125% South Asian · 114/91,088 alleles

Filtering AF 0.107% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0994%

Overall 0.00905% 146/1,614,144 alleles · rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.125%	799
Remaining individualsnot grpmax-eligible	0.0128%	7,814
Finnishnot grpmax-eligible	0.00625%	15,991
African / African-American	0.004%	25,017
East Asian	0.00223%	44,886
European (non-Finnish)	0.00136%	73,752

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: SMARCB1
Protein: p.Arg366=
Coding: c.1098C>T
MANE Select: NM_003073
dbSNP: rs562018506
Type: single nucleotide variant
Location: chr22:23833683 (GRCh38)
Gene constraint: LOEUF 0.221 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 80.77 · 17 PDB
Residue 366: a UniProt-annotated variant site (in css3); an α-helix

Full SMARCB1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

hereditary neoplastic syndrome — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

SMARCB1 p.Arg366Cys Pathogenic/Likely pathogenic ★★ same residue
SMARCB1 p.Arg366Ser Likely pathogenic ★★ same residue
SMARCB1 p.Arg366Gly Likely pathogenic ★ same residue
SMARCB1 p.Arg366His Uncertain significance ★ ⚠ same residue
SMARCB1 c.795+1G>A Likely pathogenic ★★ same condition
SMARCB1 c.93+1G>A Likely pathogenic ★★ same condition
SMARCB1 c.986+1G>A Likely pathogenic ★★ same condition
SMARCB1 c.*82C>T 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/smarcb1-p-arg366 (accessed [today's date]).

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