Is SMARCA2 p.Gln296Pro (c.887A>C) pathogenic?

SMARCA2 p.Gln296Pro (c.887A>C) is classified Conflicting classifications of pathogenicity in SMARCA2 (ClinVar, Conflicting submitters, 3 submitters; last evaluated 2026-01-08). AlphaMissense: likely benign (0.0429); Ultra-rare (popmax 0.0995%, sas); Associated with Inborn genetic diseases.

How common is SMARCA2 p.Gln296Pro (c.887A>C) in the general population?

SMARCA2 p.Gln296Pro (c.887A>C) is ultra-rare (popmax 0.0995%, sas) (gnomAD).

What do computational predictors say about SMARCA2 p.Gln296Pro (c.887A>C)?

AlphaMissense predicts likely benign (score 0.0429) — an in-silico prediction, not a clinical call.

SMARCA2 p.Gln296Pro

Q: What condition is associated with SMARCA2 p.Gln296Pro (c.887A>C)?

SMARCA2 p.Gln296Pro (c.887A>C) is associated with Inborn genetic diseases, intellectual disability-sparse hair-brachydactyly syndrome, blepharophimosis-impaired intellectual development syndrome (ClinVar).

c.887A>C · rs753868549 · VCV588983

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 3 submitters

AlphaMissense

likely benign

0.0429 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0995%, sas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.0429	likely benign
REVEL	0.151	moderately benign-leaning
SaProt	LLR -4.06	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 2.5	GERP -0.6, phastCons 1
Regional constraint	o/e 1.18	unconstrained · MANE · 7,571 bp · p 0.073 · regional, not allelic
Overall
CADD	17.25	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 0.0995% South Asian · 29/29,156 alleles

Filtering AF 0.0711% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0615%

Overall 0.00294% 32/1,086,984 alleles · ultra-rare exomes 23/940,490 · genomes 9/146,494 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0995%	1,005
Remaining individualsnot grpmax-eligible	0.00876%	11,421

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.Gln296Pro
Coding: c.887A>C
MANE Select: NM_003070
dbSNP: rs753868549
Type: single nucleotide variant
Location: chr9:2047325 (GRCh38)
Gene constraint: LOEUF 0.317 · pLI 1.00 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 66.06 · 32 PDB
Residue 296: the 'disordered' region

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

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: intellectual disability-sparse hair-brachydactyly syndrome blepharophimosis-impaired intellectual development syndrome

Similar variants

SMARCA2 p.Gln296Arg Uncertain significance ★ ⚠ same residue
SMARCA2 p.Ala1138Pro Pathogenic/Likely pathogenic ★★ same condition
SMARCA2 p.Ala1160Gly Pathogenic ★★ same condition
SMARCA2 p.Ala1201Val Pathogenic/Likely pathogenic ★★ same condition
SMARCA2 p.Arg1105Cys Pathogenic ★★ same condition
SMARCA2 p.Arg1105His Pathogenic ★★ same condition
SMARCA2 p.Arg1105Pro Pathogenic/Likely pathogenic ★★ same condition
SMARCA2 p.Arg1159Gln 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-gln296pro (accessed [today's date]).

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