Is SMARCE1 p.Val396= (c.1188G>A) pathogenic?

SMARCE1 p.Val396= (c.1188G>A) is classified Likely benign in SMARCE1 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-10-05). Very rare (popmax 0.00017%, nfe); Associated with hereditary neoplastic syndrome.

What condition is associated with SMARCE1 p.Val396= (c.1188G>A)?

SMARCE1 p.Val396= (c.1188G>A) is associated with hereditary neoplastic syndrome (ClinVar).

How common is SMARCE1 p.Val396= (c.1188G>A) in the general population?

SMARCE1 p.Val396= (c.1188G>A) is very rare (popmax 0.00017%, nfe) (gnomAD).

SMARCE1 p.Val396=

c.1188G>A · rs2508592472 · VCV1744068

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00017%, nfe)

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 0.43	GERP 1.1, phastCons 0.99
Overall
CADD	6.25	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00017% European (non-Finnish) · 2/1,179,826 alleles

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

Overall 0.000124% 2/1,613,850 alleles · very rare exomes 2/1,461,558 · genomes 0/152,292 · 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.Val396=
Coding: c.1188G>A
MANE Select: NM_003079
dbSNP: rs2508592472
Type: single nucleotide variant
Location: chr17:40628833 (GRCh38)
Gene constraint: LOEUF 0.318 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 70.72 · 8 PDB
Residue 396: the 'disordered' region

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.Val396Leu Conflicting classifications of pathogenicity ★ ⚠ same residue
SMARCE1 p.Val396Met Conflicting classifications of pathogenicity ★ ⚠ same residue
SMARCE1 p.Val396fs 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

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-val396 (accessed [today's date]).

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