Is SMARCA4 p.Pro913= (c.2739G>A) pathogenic?

SMARCA4 p.Pro913= (c.2739G>A) is classified Benign/Likely benign in SMARCA4 (ClinVar, Multiple submitters, 7 submitters; last evaluated 2026-01-31). Rare (popmax 0.116%, eas); Associated with hereditary neoplastic syndrome.

What condition is associated with SMARCA4 p.Pro913= (c.2739G>A)?

SMARCA4 p.Pro913= (c.2739G>A) is associated with hereditary neoplastic syndrome, rhabdoid tumor predisposition syndrome 2, intellectual disability, autosomal dominant 16 (ClinVar).

How common is SMARCA4 p.Pro913= (c.2739G>A) in the general population?

SMARCA4 p.Pro913= (c.2739G>A) is rare (popmax 0.116%, eas) (gnomAD).

SMARCA4 p.Pro913=

c.2739G>A · rs183695281 · VCV238414

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 7 submitters

gnomAD v4.1

Rare

rare (popmax 0.116%, eas)

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 -12	GERP -4.4
Overall
CADD	0.077	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.116% East Asian · 52/44,890 alleles

Filtering AF 0.0906% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0817%

Overall 0.00589% 95/1,613,730 alleles · rare exomes 74/1,461,346 · genomes 21/152,384 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.116%	863
African / African-American	0.024%	4,171
Remaining individualsnot grpmax-eligible	0.0048%	20,834
Admixed American	0.00333%	30,014
Finnishnot grpmax-eligible	0.00157%	63,538
European (non-Finnish)	0.00153%	65,557
South Asian	0.0011%	91,092

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.Pro913=
Coding: c.2739G>A
MANE Select: NM_003072
dbSNP: rs183695281
Type: single nucleotide variant
Location: chr19:11021847 (GRCh38)
Gene constraint: LOEUF 0.226 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 65.38 · 31 PDB
Residue 913: a β-strand; the 'sufficient for interaction with dlx1' region; the helicase atp-binding domain

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 intellectual disability, autosomal dominant 16

Similar variants

SMARCA4 p.Pro913Leu Likely pathogenic ★★ 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-pro913 (accessed [today's date]).

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