Is SMARCA2 p.Pro33Ser (c.97C>T) pathogenic?

SMARCA2 p.Pro33Ser (c.97C>T) is classified Benign/Likely benign in SMARCA2 (ClinVar, Multiple submitters, 7 submitters; last evaluated 2025-12-24). AlphaMissense: likely benign (0.1082); Ultra-rare (popmax 0.0548%, nfe); Associated with Inborn genetic diseases.

What condition is associated with SMARCA2 p.Pro33Ser (c.97C>T)?

SMARCA2 p.Pro33Ser (c.97C>T) is associated with Inborn genetic diseases, intellectual disability-sparse hair-brachydactyly syndrome (ClinVar).

How common is SMARCA2 p.Pro33Ser (c.97C>T) in the general population?

SMARCA2 p.Pro33Ser (c.97C>T) is ultra-rare (popmax 0.0548%, nfe) (gnomAD).

What do computational predictors say about SMARCA2 p.Pro33Ser (c.97C>T)?

AlphaMissense predicts likely benign (score 0.1082) — an in-silico prediction, not a clinical call.

SMARCA2 p.Pro33Ser

c.97C>T · rs146990134 · VCV366193

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 7 submitters

AlphaMissense

likely benign

0.1082 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0548%, nfe)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.1082	likely benign
REVEL	0.391	indeterminate
SaProt	LLR -10.20	damaging
⇒ SaProt calls this damaging; AlphaMissense does not; REVEL is indeterminate.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 7.7	GERP 2.7, phastCons 1
Regional constraint	o/e 1.11	unconstrained · MANE · 11 kb · p 0.08 · regional, not allelic
Overall
CADD	24.3	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 0.0548% European (non-Finnish) · 644/1,175,502 alleles

Filtering AF 0.0513% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0499%

Overall 0.042% 675/1,605,586 alleles · ultra-rare exomes 641/1,453,328 · genomes 34/152,258 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.0548%	1,825
Remaining individualsnot grpmax-eligible	0.0322%	3,107
Finnishnot grpmax-eligible	0.011%	9,061
African / African-American	0.00535%	18,689

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.Pro33Ser
Coding: c.97C>T
MANE Select: NM_003070
dbSNP: rs146990134
Type: single nucleotide variant
Location: chr9:2029119 (GRCh38)
Gene constraint: LOEUF 0.317 · pLI 1.00 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 66.06 · 32 PDB
Residue 33: 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

Similar variants

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
SMARCA2 p.Arg1159Gly 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-pro33ser (accessed [today's date]).

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