Is SMARCA2 p.Pro153= (c.459G>A) pathogenic?

SMARCA2 p.Pro153= (c.459G>A) is classified Benign/Likely benign in SMARCA2 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2020-12-02). Ultra-rare (popmax 0.0653%, afr); Associated with intellectual disability-sparse hair-brachydactyly syndrome.

What condition is associated with SMARCA2 p.Pro153= (c.459G>A)?

SMARCA2 p.Pro153= (c.459G>A) is associated with intellectual disability-sparse hair-brachydactyly syndrome (ClinVar).

How common is SMARCA2 p.Pro153= (c.459G>A) in the general population?

SMARCA2 p.Pro153= (c.459G>A) is ultra-rare (popmax 0.0653%, afr) (gnomAD).

SMARCA2 p.Pro153=

c.459G>A · rs375996388 · VCV914397

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0653%, afr)

Conditions

intellectual disability-sparse hair-brachydactyly syndrome

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -2.9	GERP -5.1
Overall
CADD	0.501	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0653% African / African-American · 49/75,016 alleles

Filtering AF 0.0507% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0455%

Overall 0.00489% 79/1,614,102 alleles · ultra-rare exomes 43/1,461,892 · genomes 36/152,210 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0653%	1,531
Admixed American	0.02%	5,001
East Asian	0.0178%	5,611
Remaining individualsnot grpmax-eligible	0.0048%	20,835
South Asian	0.0022%	45,536
European (non-Finnish)	0.000424%	236,003

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.Pro153=
Coding: c.459G>A
MANE Select: NM_003070
dbSNP: rs375996388
Type: single nucleotide variant
Location: chr9:2039569 (GRCh38)
Gene constraint: LOEUF 0.317 · pLI 1.00 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 66.06 · 32 PDB
Residue 153: 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.Pro153Leu Conflicting classifications of pathogenicity ★ ⚠ same residue
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-pro153 (accessed [today's date]).

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