Is SMARCA4 p.Pro601= (c.1803G>A) pathogenic?

SMARCA4 p.Pro601= (c.1803G>A) is classified Benign/Likely benign in SMARCA4 (ClinVar, Multiple submitters, 7 submitters; last evaluated 2026-06-01). Rare (popmax 0.105%, amr); Associated with intellectual disability, autosomal dominant 16.

What condition is associated with SMARCA4 p.Pro601= (c.1803G>A)?

SMARCA4 p.Pro601= (c.1803G>A) is associated with intellectual disability, autosomal dominant 16, rhabdoid tumor predisposition syndrome 2, hereditary neoplastic syndrome (ClinVar).

How common is SMARCA4 p.Pro601= (c.1803G>A) in the general population?

SMARCA4 p.Pro601= (c.1803G>A) is rare (popmax 0.105%, amr) (gnomAD).

SMARCA4 p.Pro601=

c.1803G>A · rs751166438 · VCV415083

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 7 submitters

gnomAD v4.1

Rare

rare (popmax 0.105%, 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 -12	GERP -4
Overall
CADD	0.206	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.105% Admixed American · 63/60,014 alleles

Filtering AF 0.0841% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0766%

Overall 0.00979% 158/1,614,010 alleles · rare exomes 151/1,461,776 · genomes 7/152,234 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.105%	953
Remaining individualsnot grpmax-eligible	0.008%	12,497
European (non-Finnish)	0.00712%	14,047
South Asian	0.00439%	22,773
African / African-American	0.00267%	37,469

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.Pro601=
Coding: c.1803G>A
MANE Select: NM_003072
dbSNP: rs751166438
Type: single nucleotide variant
Location: chr19:10996535 (GRCh38)
Gene constraint: LOEUF 0.226 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 65.38 · 31 PDB
Residue 601: the 'disordered' region; 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

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.Pro601Leu 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-pro601 (accessed [today's date]).

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