Is SMARCE1 p.Val80= (c.240C>G) pathogenic?

SMARCE1 p.Val80= (c.240C>G) is classified Likely benign in SMARCE1 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-05-10). Very rare (popmax 0.00134%, afr); Associated with familial meningioma.

What condition is associated with SMARCE1 p.Val80= (c.240C>G)?

SMARCE1 p.Val80= (c.240C>G) is associated with familial meningioma (ClinVar).

How common is SMARCE1 p.Val80= (c.240C>G) in the general population?

SMARCE1 p.Val80= (c.240C>G) is very rare (popmax 0.00134%, afr) (gnomAD).

How is Meningioma inherited?

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

SMARCE1 p.Val80=

c.240C>G · VCV3668497

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00134%, afr)

Conditions

familial meningioma

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 9.7	GERP 2.1, phastCons 1
Overall
CADD	17.19	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00134% African / African-American · 1/74,886 alleles

Overall 6.21e-05% 1/1,610,590 alleles · very rare exomes 1/1,458,370 · genomes 0/152,220 · 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.Val80=
Coding: c.240C>G
MANE Select: NM_003079
Type: single nucleotide variant
Location: chr17:40636524 (GRCh38)
Gene constraint: LOEUF 0.318 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 70.72 · 8 PDB
Residue 80: a DNA-binding region; an α-helix

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.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
SMARCE1 p.Glu165Ter Pathogenic ★★ same condition
SMARCE1 c.1027+5C>G Uncertain significance ★★ 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-val80 (accessed [today's date]).

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