Is SMARCA4 p.Leu796= (c.2388C>T) pathogenic?

SMARCA4 p.Leu796= (c.2388C>T) is classified Benign in SMARCA4 (ClinVar, Multiple submitters, 14 submitters; last evaluated 2026-02-04). Low-frequency (popmax 4.57%, sas); Associated with intellectual disability, autosomal dominant 16.

What condition is associated with SMARCA4 p.Leu796= (c.2388C>T)?

SMARCA4 p.Leu796= (c.2388C>T) is associated with intellectual disability, autosomal dominant 16, rhabdoid tumor predisposition syndrome 2, hereditary neoplastic syndrome (ClinVar).

How common is SMARCA4 p.Leu796= (c.2388C>T) in the general population?

SMARCA4 p.Leu796= (c.2388C>T) is low-frequency (popmax 4.57%, sas) (gnomAD).

SMARCA4 p.Leu796=

c.2388C>T · rs28997580 · VCV220858

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 14 submitters

gnomAD v4.1

Rare

low-frequency (popmax 4.57%, sas)

Conditions

intellectual disability, autosomal dominant 16

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 0.57	GERP -1.5, phastCons 1
Overall
CADD	11.16	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 4.57% South Asian · 4,161/91,090 alleles

Filtering AF 4.45% ClinGen BA1/BS1 input FAF95, joint · FAF99 4.4%

Overall 0.965% 15,571/1,614,174 alleles · low-frequency

Ancestry group	Frequency	1 in
South Asiangrpmax	4.57%	22
Remaining individualsnot grpmax-eligible	0.966%	103
European (non-Finnish)	0.866%	115
Middle Eastern	0.676%	148
Finnishnot grpmax-eligible	0.347%	288
Admixed American	0.29%	345
African / African-American	0.139%	722
Ashkenazi Jewishnot grpmax-eligible	0.0743%	1,346
East Asian	0.0579%	1,726

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: SMARCA4
Protein: p.Leu796=
Coding: c.2388C>T
MANE Select: NM_003072
dbSNP: rs28997580
Type: single nucleotide variant
Location: chr19:11013062 (GRCh38)
Gene constraint: LOEUF 0.226 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 65.38 · 31 PDB
Residue 796: the helicase atp-binding domain; an α-helix

Full SMARCA4 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

intellectual disability, autosomal dominant 16 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: rhabdoid tumor predisposition syndrome 2 hereditary neoplastic syndrome Coffin-Siris syndrome otosclerosis 12

Similar variants

SMARCA4 p.Leu796Phe Uncertain significance ★ ⚠ 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-leu796 (accessed [today's date]).

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