Is SMARCA4 p.Val576= (c.1728C>G) pathogenic?

SMARCA4 p.Val576= (c.1728C>G) is classified Likely benign in SMARCA4 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2023-04-28). Absent from gnomAD v4.1; Associated with hereditary neoplastic syndrome.

What condition is associated with SMARCA4 p.Val576= (c.1728C>G)?

SMARCA4 p.Val576= (c.1728C>G) is associated with hereditary neoplastic syndrome, rhabdoid tumor predisposition syndrome 2 (ClinVar).

How common is SMARCA4 p.Val576= (c.1728C>G) in the general population?

SMARCA4 p.Val576= (c.1728C>G) is absent from gnomAD v4.1 (gnomAD).

SMARCA4 p.Val576=

c.1728C>G · rs1060504461 · VCV1955421

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

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	<0.2	all four deltas below 0.2 · C>A here scores Δ0.45 · evaluated, not missing
Constraint at this position
Conservation	phyloP -14	GERP -4.1
Overall
CADD	0.256	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: SMARCA4
Protein: p.Val576=
Coding: c.1728C>G
MANE Select: NM_003072
dbSNP: rs1060504461
Type: single nucleotide variant
Location: chr19:10996347 (GRCh38)
Gene constraint: LOEUF 0.226 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 65.38 · 31 PDB
Residue 576: the 'rna-binding region which is sufficient for binding to lncrna evf2' region

Full SMARCA4 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

Also linked: rhabdoid tumor predisposition syndrome 2

Similar variants

SMARCA4 p.Val576Phe Conflicting classifications of pathogenicity ★ ⚠ same residue
SMARCA4 c.1943+1G>A Likely pathogenic ★★ same condition
SMARCA4 c.2274+1G>T Likely pathogenic ★★ same condition
SMARCA4 c.2438+1G>A Pathogenic/Likely pathogenic ★★ same condition
SMARCA4 c.3216-1G>C Likely pathogenic ★★ same condition
SMARCA4 c.3216-2A>G Likely pathogenic ★★ same condition
SMARCA4 c.3546+1G>A Likely pathogenic ★★ same condition
SMARCA4 c.3774+2T>A 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/smarca4-p-val576 (accessed [today's date]).

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