Is SMARCB1 p.Ser299= (c.897G>A) pathogenic?

SMARCB1 p.Ser299= (c.897G>A) is classified Benign in SMARCB1 (ClinVar, Multiple submitters, 13 submitters; last evaluated 2026-02-04). Common (popmax 17.6%, sas) — too common for a highly-penetrant pathogenic allele; Associated with rhabdoid tumor predisposition syndrome 1.

What condition is associated with SMARCB1 p.Ser299= (c.897G>A)?

SMARCB1 p.Ser299= (c.897G>A) is associated with rhabdoid tumor predisposition syndrome 1, hereditary neoplastic syndrome, SMARCB1-related schwannomatosis (ClinVar).

How is Rhabdoid tumor predisposition syndrome inherited?

Typically Autosomal dominant (Orphanet). A genetic counselor can assess individual risk for a family.

SMARCB1 p.Ser299=

Q: How common is SMARCB1 p.Ser299= (c.897G>A) in the general population?

SMARCB1 p.Ser299= (c.897G>A) is common (popmax 17.6%, sas) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.897G>A · rs2229354 · VCV126368

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 13 submitters

gnomAD v4.1

Common

common (popmax 17.6%, sas) — too common for a highly-penetrant pathogenic allele

Conditions

rhabdoid tumor predisposition syndrome 1

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 -15	GERP -3.5
Overall
CADD	0.13	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 17.6% South Asian · 15,988/91,078 alleles

Filtering AF 17.3% ClinGen BA1/BS1 input FAF95, joint · FAF99 17.2%

Overall 11.3% 182,809/1,614,008 alleles · common

Ancestry group	Frequency	1 in
South Asiangrpmax	17.6%	6
Middle Eastern	15.2%	7
Amishnot grpmax-eligible	14%	7
Finnishnot grpmax-eligible	12.8%	8
Remaining individualsnot grpmax-eligible	11.7%	9
European (non-Finnish)	11.3%	9
Ashkenazi Jewishnot grpmax-eligible	10.6%	9
African / African-American	8.56%	12
Admixed American	8.12%	12
East Asian	4.93%	20

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.Ser299=
Coding: c.897G>A
MANE Select: NM_003073
dbSNP: rs2229354
Type: single nucleotide variant
Location: chr22:23825326 (GRCh38)
Gene constraint: LOEUF 0.221 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 80.77 · 17 PDB
Residue 299: an α-helix; the '2 x approximate tandem repeats' region

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

Disease context

rhabdoid tumor predisposition syndrome 1 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: hereditary neoplastic syndrome SMARCB1-related schwannomatosis

For Rhabdoid tumor predisposition syndrome (Orphanet):

Inheritance: Autosomal dominant
Onset: Childhood

Similar variants

SMARCB1 p.Ser299Leu Conflicting classifications of pathogenicity ★ ⚠ 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
SMARCB1 p.Arg158Ter Pathogenic ★★ same condition
SMARCB1 p.Arg201Ter Pathogenic ★★ same condition
SMARCB1 p.Arg374Gln 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-ser299 (accessed [today's date]).

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