Is SMARCA4 p.Pro919= (c.2757C>T) pathogenic?

SMARCA4 p.Pro919= (c.2757C>T) is classified Benign/Likely benign in SMARCA4 (ClinVar, Multiple submitters, 11 submitters; last evaluated 2026-05-01). Rare (popmax 0.847%, afr); Associated with Coffin-Siris syndrome.

What condition is associated with SMARCA4 p.Pro919= (c.2757C>T)?

SMARCA4 p.Pro919= (c.2757C>T) is associated with Coffin-Siris syndrome, rhabdoid tumor predisposition syndrome 2, intellectual disability, autosomal dominant 16 (ClinVar).

How common is SMARCA4 p.Pro919= (c.2757C>T) in the general population?

SMARCA4 p.Pro919= (c.2757C>T) is rare (popmax 0.847%, afr) (gnomAD).

SMARCA4 p.Pro919=

c.2757C>T · rs113955216 · VCV212243

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 11 submitters

gnomAD v4.1

Rare

rare (popmax 0.847%, afr)

Conditions

Coffin-Siris 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 -10	GERP -4.4
Overall
CADD	7.21	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.847% African / African-American · 636/75,060 alleles

Filtering AF 0.793% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.771%

Overall 0.0513% 828/1,613,788 alleles · rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.847%	118
Middle Eastern	0.248%	404
Remaining individualsnot grpmax-eligible	0.122%	822
Ashkenazi Jewishnot grpmax-eligible	0.0676%	1,480
Admixed American	0.0483%	2,070
South Asian	0.00549%	18,218
East Asian	0.00446%	22,444
European (non-Finnish)	0.00381%	26,223

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.Pro919=
Coding: c.2757C>T
MANE Select: NM_003072
dbSNP: rs113955216
Type: single nucleotide variant
Location: chr19:11021865 (GRCh38)
Gene constraint: LOEUF 0.226 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 65.38 · 31 PDB
Residue 919: an α-helix; the helicase atp-binding domain

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

Disease context

Coffin-Siris syndrome — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: rhabdoid tumor predisposition syndrome 2 intellectual disability, autosomal dominant 16 hereditary neoplastic syndrome

Similar variants

SMARCA4 p.Pro919Ser 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-pro919 (accessed [today's date]).

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