Is SMARCE1 p.Val84= (c.252A>G) pathogenic?

SMARCE1 p.Val84= (c.252A>G) is classified Likely benign in SMARCE1 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-05-17). Absent from gnomAD v4.1; Associated with hereditary neoplastic syndrome.

What condition is associated with SMARCE1 p.Val84= (c.252A>G)?

SMARCE1 p.Val84= (c.252A>G) is associated with hereditary neoplastic syndrome (ClinVar).

How common is SMARCE1 p.Val84= (c.252A>G) in the general population?

SMARCE1 p.Val84= (c.252A>G) is absent from gnomAD v4.1 (gnomAD).

SMARCE1 p.Val84=

c.252A>G · VCV3958601

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Absent

absent from gnomAD v4.1

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 1.2	GERP -0.95, phastCons 1
Overall
CADD	9.565	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: SMARCE1
Protein: p.Val84=
Coding: c.252A>G
MANE Select: NM_003079
Type: single nucleotide variant
Location: chr17:40636512 (GRCh38)
Gene constraint: LOEUF 0.318 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 70.72 · 8 PDB
Residue 84: a DNA-binding region; an α-helix

Full SMARCE1 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

SMARCE1 p.Val84Ile Uncertain significance ★ ⚠ same residue
SMARCE1 p.Val84Ala Uncertain significance ★ ⚠ same residue
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

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-val84 (accessed [today's date]).

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