Is SMARCB1 p.Phe17= (c.51C>T) pathogenic?

SMARCB1 p.Phe17= (c.51C>T) is classified Likely benign in SMARCB1 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-06-10). Very rare (popmax 8.49e-05%, nfe); Associated with hereditary neoplastic syndrome.

What condition is associated with SMARCB1 p.Phe17= (c.51C>T)?

SMARCB1 p.Phe17= (c.51C>T) is associated with hereditary neoplastic syndrome (ClinVar).

How common is SMARCB1 p.Phe17= (c.51C>T) in the general population?

SMARCB1 p.Phe17= (c.51C>T) is very rare (popmax 8.49e-05%, nfe) (gnomAD).

SMARCB1 p.Phe17=

c.51C>T · rs2517652662 · VCV2562339

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 8.49e-05%, 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 4.6	GERP 1.4, phastCons 1
Overall
CADD	14.82	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 8.49e-05% European (non-Finnish) · 1/1,177,228 alleles

Overall 6.22e-05% 1/1,608,996 alleles · very rare exomes 1/1,456,802 · genomes 0/152,194 · 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.Phe17=
Coding: c.51C>T
MANE Select: NM_003073
dbSNP: rs2517652662
Type: single nucleotide variant
Location: chr22:23787220 (GRCh38)
Gene constraint: LOEUF 0.221 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 80.77 · 17 PDB
Residue 17: the 'dna-binding' region

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-phe17 (accessed [today's date]).

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