Is SMARCA4 p.Pro244Arg (c.731C>G) pathogenic?

SMARCA4 p.Pro244Arg (c.731C>G) is classified Uncertain significance in SMARCA4 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2024-03-01). AlphaMissense: likely benign (0.2489); Very rare (popmax 0.00245%, eas); Associated with hereditary neoplastic syndrome.

What condition is associated with SMARCA4 p.Pro244Arg (c.731C>G)?

SMARCA4 p.Pro244Arg (c.731C>G) is associated with hereditary neoplastic syndrome, rhabdoid tumor predisposition syndrome 2 (ClinVar).

How common is SMARCA4 p.Pro244Arg (c.731C>G) in the general population?

SMARCA4 p.Pro244Arg (c.731C>G) is very rare (popmax 0.00245%, eas) (gnomAD).

What do computational predictors say about SMARCA4 p.Pro244Arg (c.731C>G)?

AlphaMissense predicts likely benign (score 0.2489) — an in-silico prediction, not a clinical call.

SMARCA4 p.Pro244Arg

c.731C>G · rs587778683 · VCV826965

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.2489 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00245%, eas)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

hereditary neoplastic syndrome

Computational evidence

Protein change
AlphaMissense	0.2489	likely benign
REVEL	0.393	indeterminate
SaProt	LLR -11.40	damaging
⇒ SaProt calls this damaging; AlphaMissense does not; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 5.6	GERP 1.6, phastCons 1
Regional constraint	o/e 0.93	unconstrained · MANE · 2,911 bp · p 0.24 · regional, not allelic
Overall
CADD	22.5	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00245% East Asian · 1/40,886 alleles

Overall 7.22e-05% 1/1,385,402 alleles · very rare

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.Pro244Arg
Coding: c.731C>G
MANE Select: NM_003072
dbSNP: rs587778683
Type: single nucleotide variant
Location: chr19:10986564 (GRCh38)
Gene constraint: LOEUF 0.226 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 65.38 · 31 PDB
Residue 244: 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

hereditary neoplastic syndrome — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: rhabdoid tumor predisposition syndrome 2

Similar variants

SMARCA4 p.Pro244Ser Uncertain significance ★★ ⚠ same residue
SMARCA4 p.Pro244= Benign/Likely benign ★★ same residue
SMARCA4 p.Pro244Leu Conflicting classifications of pathogenicity ★ ⚠ same residue
SMARCA4 p.Pro244_Ala245insGlyProGlyProGlyProGlyProGlyProGlyProGlyProGlyPro Uncertain significance ★★ same residue
SMARCA4 p.Pro244_Ala245insGlyPro Uncertain significance ★ same residue
SMARCA4 p.Pro244_Ala245insGlyProGlyPro Uncertain significance ★ same residue
SMARCA4 p.Pro244_Ala245insGlyProGlyProGlyProGlyPro Uncertain significance ★ same residue
SMARCA4 p.Pro244_Ala245insGlyProGlyProGlyProGlyProGlyPro Uncertain significance ★ same residue

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-pro244arg (accessed [today's date]).

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