Is SMARCA2 p.Pro292Arg (c.875C>G) pathogenic?

SMARCA2 p.Pro292Arg (c.875C>G) is classified Benign in SMARCA2 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-06-17). AlphaMissense: likely benign (0.1931); Absent from gnomAD v4.1.

How common is SMARCA2 p.Pro292Arg (c.875C>G) in the general population?

SMARCA2 p.Pro292Arg (c.875C>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about SMARCA2 p.Pro292Arg (c.875C>G)?

AlphaMissense predicts likely benign (score 0.1931) — an in-silico prediction, not a clinical call.

SMARCA2 p.Pro292Arg

c.875C>G · VCV3638941

Benign Single submitter

Classification

Benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1931 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1931	likely benign
REVEL	0.208	benign-leaning
SaProt	LLR -9.98	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 3.5	GERP 1.8, phastCons 0.9
Regional constraint	o/e 1.18	unconstrained · MANE · 7,571 bp · p 0.073 · regional, not allelic
Overall
CADD	23.1	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

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.Pro292Arg
Coding: c.875C>G
MANE Select: NM_003070
Type: single nucleotide variant
Location: chr9:2047313 (GRCh38)
Gene constraint: LOEUF 0.317 · pLI 1.00 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 66.06 · 32 PDB
Residue 292: the 'disordered' region

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

Similar variants

SMARCA2 p.Pro292Ser Uncertain significance ★★ ⚠ same residue
SMARCA2 p.Pro292Leu Conflicting classifications of pathogenicity ★ ⚠ same residue
SMARCA2 p.Pro292= Likely benign ★ 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
SMARCA2 p.Arg1105Cys 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-pro292arg (accessed [today's date]).

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