Is SMARCE1 p.Pro175= (c.525T>C) pathogenic?

SMARCE1 p.Pro175= (c.525T>C) is classified Benign/Likely benign in SMARCE1 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2025-05-14). Very rare (popmax 0.000515%, nfe); Associated with familial meningioma.

What condition is associated with SMARCE1 p.Pro175= (c.525T>C)?

SMARCE1 p.Pro175= (c.525T>C) is associated with familial meningioma, rhabdoid tumor predisposition syndrome 1, hereditary neoplastic syndrome (ClinVar).

How common is SMARCE1 p.Pro175= (c.525T>C) in the general population?

SMARCE1 p.Pro175= (c.525T>C) is very rare (popmax 0.000515%, nfe) (gnomAD).

How is Meningioma inherited?

Typically Not applicable (Orphanet). A genetic counselor can assess individual risk for a family.

SMARCE1 p.Pro175=

c.525T>C · rs773720929 · VCV414255

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

gnomAD v4.1

Rare

very rare (popmax 0.000515%, nfe)

Conditions

familial meningioma

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.036	moderately benign-leaning
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 0.75	GERP -0.39, phastCons 0.96
Overall
CADD	10.02	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.000515% European (non-Finnish) · 6/1,164,080 alleles

Filtering AF 0.000185% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000122%

Overall 0.00038% 6/1,577,502 alleles · very rare exomes 6/1,425,186 · genomes 0/152,316 · 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: SMARCE1
Protein: p.Pro175=
Coding: c.525T>C
MANE Select: NM_003079
dbSNP: rs773720929
Type: single nucleotide variant
Location: chr17:40635947 (GRCh38)
Gene constraint: LOEUF 0.318 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 70.72 · 8 PDB
Residue 175: the 'disordered' region

Full SMARCE1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

familial meningioma — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: rhabdoid tumor predisposition syndrome 1 hereditary neoplastic syndrome SMARCB1-related schwannomatosis

For Meningioma (Orphanet):

Inheritance: Not applicable
Onset: All ages
Prevalence: 1-9 / 100 000 (Germany)

Similar variants

SMARCE1 p.Pro175Ala Uncertain significance ★ ⚠ same residue
SMARCE1 p.Pro175Thr Uncertain significance ★ ⚠ same residue
SMARCE1 p.Arg105Gln Pathogenic/Likely pathogenic ★★ same condition
SMARCE1 p.Arg158Ter Pathogenic ★★ same condition
SMARCE1 p.Arg239Ter Pathogenic ★★ same condition
SMARCE1 p.Arg251Ter Pathogenic/Likely pathogenic ★★ same condition
SMARCE1 p.Gln225Ter Pathogenic ★★ same condition
SMARCE1 p.Glu110Ter 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/smarce1-p-pro175 (accessed [today's date]).

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