Is SMARCE1 p.Arg299= (c.897G>A) pathogenic?

SMARCE1 p.Arg299= (c.897G>A) is classified Likely benign in SMARCE1 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-06-14). Very rare (popmax 0.00167%, amr); Associated with familial meningioma.

What condition is associated with SMARCE1 p.Arg299= (c.897G>A)?

SMARCE1 p.Arg299= (c.897G>A) is associated with familial meningioma (ClinVar).

How common is SMARCE1 p.Arg299= (c.897G>A) in the general population?

SMARCE1 p.Arg299= (c.897G>A) is very rare (popmax 0.00167%, amr) (gnomAD).

How is Meningioma inherited?

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

SMARCE1 p.Arg299=

c.897G>A · rs754006294 · VCV1583491

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00167%, amr)

Conditions

familial meningioma

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.028	moderately benign-leaning
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 1.1	GERP 2.1, phastCons 1
Overall
CADD	11.22	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00167% Admixed American · 1/60,018 alleles

Filtering AF 2.8e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.1e-05%

Overall 0.000205% 3/1,461,808 alleles · very rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00167%	60,018
European (non-Finnish)	0.000169%	590,009

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.Arg299=
Coding: c.897G>A
MANE Select: NM_003079
dbSNP: rs754006294
Type: single nucleotide variant
Location: chr17:40630844 (GRCh38)
Gene constraint: LOEUF 0.318 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 70.72 · 8 PDB
Residue 299: 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

For Meningioma (Orphanet):

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

Similar variants

SMARCE1 p.Arg299Met Uncertain significance ★ ⚠ same residue
SMARCE1 p.Arg299Ser Uncertain significance ★ ⚠ same residue
SMARCE1 p.Arg299Thr Uncertain significance ★ ⚠ same residue
SMARCE1 p.Arg299Lys 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

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-arg299 (accessed [today's date]).

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