Is SMARCB1 p.Pro136= (c.408C>T) pathogenic?

SMARCB1 p.Pro136= (c.408C>T) is classified Likely benign in SMARCB1 (ClinVar, Single submitter, 1 submitter; last evaluated 2018-06-27). Very rare (popmax 0.000254%, nfe); Associated with hereditary neoplastic syndrome.

What condition is associated with SMARCB1 p.Pro136= (c.408C>T)?

SMARCB1 p.Pro136= (c.408C>T) is associated with hereditary neoplastic syndrome (ClinVar).

How common is SMARCB1 p.Pro136= (c.408C>T) in the general population?

SMARCB1 p.Pro136= (c.408C>T) is very rare (popmax 0.000254%, nfe) (gnomAD).

SMARCB1 p.Pro136=

c.408C>T · rs1601401844 · VCV824582

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.000254%, nfe)

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 0.78	GERP 0.22, phastCons 1
Overall
CADD	10.95	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.000254% European (non-Finnish) · 3/1,180,008 alleles

Filtering AF 6.8e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.9e-05%

Overall 0.000186% 3/1,614,170 alleles · very rare exomes 3/1,461,866 · genomes 0/152,304 · joint denominator

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.Pro136=
Coding: c.408C>T
MANE Select: NM_003073
dbSNP: rs1601401844
Type: single nucleotide variant
Location: chr22:23800989 (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

Similar variants

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
SMARCB1 p.Arg377His 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-pro136 (accessed [today's date]).

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