Is SMARCA2 p.Pro197Arg (c.590C>G) pathogenic?

SMARCA2 p.Pro197Arg (c.590C>G) is classified Uncertain significance in SMARCA2 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2024-09-28). AlphaMissense: ambiguous (0.4603); Absent from gnomAD v4.1; Associated with SMARCA2-related disorder.

What condition is associated with SMARCA2 p.Pro197Arg (c.590C>G)?

SMARCA2 p.Pro197Arg (c.590C>G) is associated with SMARCA2-related disorder (ClinVar).

How common is SMARCA2 p.Pro197Arg (c.590C>G) in the general population?

SMARCA2 p.Pro197Arg (c.590C>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about SMARCA2 p.Pro197Arg (c.590C>G)?

AlphaMissense predicts ambiguous (score 0.4603) — an in-silico prediction, not a clinical call.

SMARCA2 p.Pro197Arg

c.590C>G · VCV3346845

Uncertain significance No assertion criteria

Classification

Uncertain significance

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.4603 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

2/2 damaging

REVEL, SaProt · AlphaMissense indeterminate

Conditions

SMARCA2-related disorder

Computational evidence

Protein change
AlphaMissense	0.4603	ambiguous
REVEL	0.801	moderately pathogenic-leaning
SaProt	LLR -10.15	damaging
⇒ REVEL and SaProt both call this damaging; AlphaMissense is indeterminate.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 6.4	GERP 1.6, phastCons 1
Regional constraint	o/e 0.45	unconstrained · MANE · 138 bp · p 5e-05 · regional, not allelic
Overall
CADD	24.5	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

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.Pro197Arg
Coding: c.590C>G
MANE Select: NM_003070
Type: single nucleotide variant
Location: chr9:2039700 (GRCh38)
Gene constraint: LOEUF 0.317 · pLI 1.00 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 66.06 · 32 PDB
Residue 197: the qlq domain

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

Disease context

SMARCA2-related disorder

Similar variants

SMARCA2 p.Pro197= Likely benign ★★ same residue
SMARCA2 p.Arg1159Gln Pathogenic/Likely pathogenic ★★ same condition
SMARCA2 p.Arg1162Cys Pathogenic/Likely pathogenic ★★ same condition
SMARCA2 p.Arg855Gln Pathogenic ★★ same condition
SMARCA2 p.Arg937His Pathogenic/Likely pathogenic ★★ same condition
SMARCA2 p.Ile518Thr Likely pathogenic ★★ same condition
SMARCA2 p.Pro883Leu Pathogenic ★★ same condition
SMARCA2 p.Ser783Leu Pathogenic/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/smarca2-p-pro197arg (accessed [today's date]).

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