Is SMARCA4 p.Ser147= (c.441C>T) pathogenic?

SMARCA4 p.Ser147= (c.441C>T) is classified Benign/Likely benign in SMARCA4 (ClinVar, Multiple submitters, 8 submitters; last evaluated 2026-01-31). Rare (popmax 0.44%, amr); Associated with intellectual disability, autosomal dominant 16.

What condition is associated with SMARCA4 p.Ser147= (c.441C>T)?

SMARCA4 p.Ser147= (c.441C>T) is associated with intellectual disability, autosomal dominant 16, rhabdoid tumor predisposition syndrome 2, hereditary neoplastic syndrome (ClinVar).

How common is SMARCA4 p.Ser147= (c.441C>T) in the general population?

SMARCA4 p.Ser147= (c.441C>T) is rare (popmax 0.44%, amr) (gnomAD).

SMARCA4 p.Ser147=

c.441C>T · rs201372858 · VCV415069

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 8 submitters

gnomAD v4.1

Rare

rare (popmax 0.44%, amr)

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	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP -2.8	GERP -4.1
Overall
CADD	4.972	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.44% Admixed American · 264/60,024 alleles

Filtering AF 0.396% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.379%

Overall 0.0194% 313/1,613,868 alleles · rare exomes 285/1,461,536 · genomes 28/152,332 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.44%	227
Remaining individualsnot grpmax-eligible	0.0176%	5,682
Middle Eastern	0.0165%	6,062
East Asian	0.0134%	7,480
African / African-American	0.012%	8,340
South Asian	0.00439%	22,772
European (non-Finnish)	0.00153%	65,556

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.Ser147=
Coding: c.441C>T
MANE Select: NM_003072
dbSNP: rs201372858
Type: single nucleotide variant
Location: chr19:10986274 (GRCh38)
Gene constraint: LOEUF 0.226 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 65.38 · 31 PDB
Residue 147: the 'necessary for interaction with ss18l1/crest' region; the 'disordered' region

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

Similar variants

SMARCA4 p.Ser147Ala Uncertain significance ★ ⚠ same residue
SMARCA4 p.Ser147Tyr 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

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-ser147 (accessed [today's date]).

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