Is SMARCA2 p.Pro609= (c.1827A>G) pathogenic?

SMARCA2 p.Pro609= (c.1827A>G) is classified Benign in SMARCA2 (ClinVar, Multiple submitters, 7 submitters; last evaluated 2026-02-03). Common (popmax 15.4%, amr) — too common for a highly-penetrant pathogenic allele; Associated with Inborn genetic diseases.

What condition is associated with SMARCA2 p.Pro609= (c.1827A>G)?

SMARCA2 p.Pro609= (c.1827A>G) is associated with Inborn genetic diseases, intellectual disability-sparse hair-brachydactyly syndrome (ClinVar).

SMARCA2 p.Pro609=

Q: How common is SMARCA2 p.Pro609= (c.1827A>G) in the general population?

SMARCA2 p.Pro609= (c.1827A>G) is common (popmax 15.4%, amr) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.1827A>G · rs13288443 · VCV126345

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 7 submitters

gnomAD v4.1

Common

common (popmax 15.4%, amr) — too common for a highly-penetrant pathogenic allele

Conditions

Inborn genetic diseases

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 -0.91	GERP -5.4
Overall
CADD	6.28	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 15.4% Admixed American · 9,214/60,010 alleles

Filtering AF 15.1% ClinGen BA1/BS1 input FAF95, joint · FAF99 15%

Overall 11.7% 188,135/1,613,946 alleles · common exomes 169,809/1,461,734 · genomes 18,326/152,212 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	15.4%	7
Finnishnot grpmax-eligible	14.9%	7
South Asian	13.8%	7
African / African-American	13%	8
European (non-Finnish)	11.5%	9
Remaining individualsnot grpmax-eligible	10.7%	9
Middle Eastern	8.12%	12
Amishnot grpmax-eligible	7.46%	13
Ashkenazi Jewishnot grpmax-eligible	7.21%	14
East Asian	4.98%	20

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.Pro609=
Coding: c.1827A>G
MANE Select: NM_003070
dbSNP: rs13288443
Type: single nucleotide variant
Location: chr9:2073292 (GRCh38)
Gene constraint: LOEUF 0.317 · pLI 1.00 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 66.06 · 32 PDB

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-pro609 (accessed [today's date]).

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