Is SMARCA2 p.Pro291Arg (c.872C>G) pathogenic?

SMARCA2 p.Pro291Arg (c.872C>G) is classified Uncertain significance in SMARCA2 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2023-05-05). AlphaMissense: likely benign (0.2443); Absent from gnomAD v4.1.

How common is SMARCA2 p.Pro291Arg (c.872C>G) in the general population?

SMARCA2 p.Pro291Arg (c.872C>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about SMARCA2 p.Pro291Arg (c.872C>G)?

AlphaMissense predicts likely benign (score 0.2443) — an in-silico prediction, not a clinical call.

SMARCA2 p.Pro291Arg

c.872C>G · rs1218396728 · VCV1878773

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.2443 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Computational evidence

Protein change
AlphaMissense	0.2443	likely benign
REVEL	0.465	indeterminate
SaProt	LLR -9.56	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL is indeterminate.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.5	GERP 1.8, phastCons 1
Regional constraint	o/e 1.18	unconstrained · MANE · 7,571 bp · p 0.073 · regional, not allelic
Overall
CADD	24.8	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

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

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: SMARCA2
Protein: p.Pro291Arg
Coding: c.872C>G
MANE Select: NM_003070
dbSNP: rs1218396728
Type: single nucleotide variant
Location: chr9:2047310 (GRCh38)
Gene constraint: LOEUF 0.317 · pLI 1.00 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 66.06 · 32 PDB
Residue 291: the 'disordered' region

Full SMARCA2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

SMARCA2 p.Pro291Leu Uncertain significance ★★ ⚠ same residue
SMARCA2 p.Pro291Ser Uncertain significance ★★ ⚠ same residue
SMARCA2 p.Pro291= Likely benign ★ same residue
SMARCA2 p.Pro291_Pro292insGlyGlyArgProSerProAlaPro Uncertain significance ★ same residue
SMARCA2 p.Ala1138Pro Pathogenic/Likely pathogenic ★★ same type
SMARCA2 p.Ala1160Gly Pathogenic ★★ same type
SMARCA2 p.Ala1201Glu Pathogenic/Likely pathogenic ★★ same type
SMARCA2 p.Ala1201Val Pathogenic/Likely pathogenic ★★ same type

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/smarca2-p-pro291arg (accessed [today's date]).

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