Is SMARCA2 p.Gln232Pro (c.695A>C) pathogenic?

SMARCA2 p.Gln232Pro (c.695A>C) is classified Benign/Likely benign in SMARCA2 (ClinVar, Multiple submitters, 7 submitters; last evaluated 2025-12-01). AlphaMissense: likely benign (0.0751); Rare (popmax 0.233%, amr); Associated with intellectual disability-sparse hair-brachydactyly syndrome.

What condition is associated with SMARCA2 p.Gln232Pro (c.695A>C)?

SMARCA2 p.Gln232Pro (c.695A>C) is associated with intellectual disability-sparse hair-brachydactyly syndrome (ClinVar).

How common is SMARCA2 p.Gln232Pro (c.695A>C) in the general population?

SMARCA2 p.Gln232Pro (c.695A>C) is rare (popmax 0.233%, amr) (gnomAD).

What do computational predictors say about SMARCA2 p.Gln232Pro (c.695A>C)?

AlphaMissense predicts likely benign (score 0.0751) — an in-silico prediction, not a clinical call.

SMARCA2 p.Gln232Pro

c.695A>C · rs143245740 · VCV366200

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 7 submitters

AlphaMissense

likely benign

0.0751 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.233%, amr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

intellectual disability-sparse hair-brachydactyly syndrome

Computational evidence

Protein change
AlphaMissense	0.0751	likely benign
REVEL	0.071	moderately benign-leaning
SaProt	LLR -8.88	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	6.899	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 0.233% Admixed American · 139/59,572 alleles

Filtering AF 0.202% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.19%

Overall 0.0853% 1,372/1,607,546 alleles · rare exomes 1,246/1,455,360 · genomes 126/152,186 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.233%	429
Remaining individualsnot grpmax-eligible	0.103%	971
European (non-Finnish)	0.098%	1,021
Middle Eastern	0.0167%	6,006
African / African-American	0.0134%	7,489
Ashkenazi Jewishnot grpmax-eligible	0.00677%	14,770
East Asian	0.00447%	22,364
Finnishnot grpmax-eligible	0.0016%	62,602

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.Gln232Pro
Coding: c.695A>C
MANE Select: NM_003070
dbSNP: rs143245740
Type: single nucleotide variant
Location: chr9:2039805 (GRCh38)
Gene constraint: LOEUF 0.317 · pLI 1.00 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 66.06 · 32 PDB
Residue 232: the 'disordered' region

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

Disease context

intellectual disability-sparse hair-brachydactyly syndrome — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

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
SMARCA2 p.Arg1159Gly Pathogenic ★★ same condition
SMARCA2 p.Arg1162Cys 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-gln232pro (accessed [today's date]).

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