Is SMARCA2 p.Gln237Pro (c.710A>C) pathogenic?

SMARCA2 p.Gln237Pro (c.710A>C) is classified Uncertain significance in SMARCA2 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-06-27). AlphaMissense: likely benign (0.0793); Very rare (popmax 0.000595%, nfe).

How common is SMARCA2 p.Gln237Pro (c.710A>C) in the general population?

SMARCA2 p.Gln237Pro (c.710A>C) is very rare (popmax 0.000595%, nfe) (gnomAD).

What do computational predictors say about SMARCA2 p.Gln237Pro (c.710A>C)?

AlphaMissense predicts likely benign (score 0.0793) — an in-silico prediction, not a clinical call.

SMARCA2 p.Gln237Pro

c.710A>C · rs1475414100 · VCV1359009

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0793 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000595%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0793	likely benign
REVEL	0.065	moderately benign-leaning
SaProt	LLR -7.70	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Regional constraint	o/e 1.18	unconstrained · MANE · 7,571 bp · p 0.073 · regional, not allelic
Overall
CADD	8.45	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

Grpmax group 0.000595% European (non-Finnish) · 7/1,177,188 alleles

Filtering AF 0.000247% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000159%

Overall 0.000435% 7/1,608,018 alleles · very rare exomes 6/1,455,918 · genomes 1/152,100 · joint denominator

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: SMARCA2
Protein: p.Gln237Pro
Coding: c.710A>C
MANE Select: NM_003070
dbSNP: rs1475414100
Type: single nucleotide variant
Location: chr9:2039820 (GRCh38)
Gene constraint: LOEUF 0.317 · pLI 1.00 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 66.06 · 32 PDB
Residue 237: the 'disordered' region

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

Similar variants

SMARCA2 p.Gln237Lys Uncertain significance ★ ⚠ same residue
SMARCA2 p.Gln237_Gln238del Benign/Likely benign ★★ same residue
SMARCA2 p.Gln237_Gln238insProGlnGln 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-gln237pro (accessed [today's date]).

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