Is SMARCE1 p.Pro45Ser (c.133C>T) pathogenic?

SMARCE1 p.Pro45Ser (c.133C>T) is classified Uncertain significance in SMARCE1 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2024-11-14). AlphaMissense: likely benign (0.1161); Absent from gnomAD v4.1; Associated with familial meningioma.

What condition is associated with SMARCE1 p.Pro45Ser (c.133C>T)?

SMARCE1 p.Pro45Ser (c.133C>T) is associated with familial meningioma, hereditary neoplastic syndrome (ClinVar).

How common is SMARCE1 p.Pro45Ser (c.133C>T) in the general population?

SMARCE1 p.Pro45Ser (c.133C>T) is absent from gnomAD v4.1 (gnomAD).

How is Meningioma inherited?

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

What do computational predictors say about SMARCE1 p.Pro45Ser (c.133C>T)?

AlphaMissense predicts likely benign (score 0.1161) — an in-silico prediction, not a clinical call.

SMARCE1 p.Pro45Ser

c.133C>T · rs1597749741 · VCV818980

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

AlphaMissense

likely benign

0.1161 · ACMG-weighted

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 1,609,960)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

familial meningioma

Computational evidence

Protein change
AlphaMissense	0.1161	likely benign
REVEL	0.265	benign-leaning
SaProt	LLR -5.95	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 2.1, phastCons 1
Regional constraint	o/e 0.33	constrained · MANE · 8,284 bp · p 1.4e-10 · regional, not allelic
Overall
CADD	25.1	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

No allele count reported in gnomAD v4.1 (AN 1,609,960). This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: SMARCE1
Protein: p.Pro45Ser
Coding: c.133C>T
MANE Select: NM_003079
dbSNP: rs1597749741
Type: single nucleotide variant
Location: chr17:40642478 (GRCh38)
Gene constraint: LOEUF 0.318 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 70.72 · 8 PDB
Residue 45: 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: hereditary neoplastic syndrome

For Meningioma (Orphanet):

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

Similar variants

SMARCE1 p.Pro45Leu Uncertain significance ★★ ⚠ same residue
SMARCE1 p.Pro45= Likely benign ★★ same residue
SMARCE1 p.Pro45Ala 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

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-pro45ser (accessed [today's date]).

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