Is SMARCB1 p.Pro146= (c.438A>G) pathogenic?

SMARCB1 p.Pro146= (c.438A>G) is classified Benign/Likely benign in SMARCB1 (ClinVar, Multiple submitters, 12 submitters; last evaluated 2026-02-04). Low-frequency (popmax 1.68%, afr); Associated with hereditary neoplastic syndrome.

What condition is associated with SMARCB1 p.Pro146= (c.438A>G)?

SMARCB1 p.Pro146= (c.438A>G) is associated with hereditary neoplastic syndrome, rhabdoid tumor predisposition syndrome 1, intellectual disability, autosomal dominant 15 (ClinVar).

How common is SMARCB1 p.Pro146= (c.438A>G) in the general population?

SMARCB1 p.Pro146= (c.438A>G) is low-frequency (popmax 1.68%, afr) (gnomAD).

SMARCB1 p.Pro146=

c.438A>G · rs35105793 · VCV239484

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 12 submitters

gnomAD v4.1

Rare

low-frequency (popmax 1.68%, afr)

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 -9.1	GERP -2.6
Overall
CADD	0.172	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 1.68% African / African-American · 1,260/75,038 alleles

Filtering AF 1.6% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.57%

Overall 0.0943% 1,522/1,614,144 alleles · low-frequency

Ancestry group	Frequency	1 in
African / African-Americangrpmax	1.68%	60
Admixed American	0.173%	577
Middle Eastern	0.148%	674
Remaining individualsnot grpmax-eligible	0.13%	772
European (non-Finnish)	0.00542%	18,437
Ashkenazi Jewishnot grpmax-eligible	0.00338%	29,604
East Asian	0.00223%	44,890
South Asian	0.0022%	45,543

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.Pro146=
Coding: c.438A>G
MANE Select: NM_003073
dbSNP: rs35105793
Type: single nucleotide variant
Location: chr22:23801019 (GRCh38)
Gene constraint: LOEUF 0.221 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 80.77 · 17 PDB

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

Also linked: rhabdoid tumor predisposition syndrome 1 intellectual disability, autosomal dominant 15 SMARCB1-related schwannomatosis

Similar variants

SMARCB1 p.Pro146Arg 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
SMARCB1 p.Arg158Ter Pathogenic ★★ same condition
SMARCB1 p.Arg201Ter Pathogenic ★★ same condition
SMARCB1 p.Arg366Cys 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-pro146 (accessed [today's date]).

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