Is SMARCA2 p.Asp82= (c.246C>T) pathogenic?

SMARCA2 p.Asp82= (c.246C>T) is classified Benign/Likely benign in SMARCA2 (ClinVar, Multiple submitters, 7 submitters; last evaluated 2025-09-28). Rare (popmax 0.495%, eas); Associated with blepharophimosis-impaired intellectual development syndrome.

What condition is associated with SMARCA2 p.Asp82= (c.246C>T)?

SMARCA2 p.Asp82= (c.246C>T) is associated with blepharophimosis-impaired intellectual development syndrome, intellectual disability-sparse hair-brachydactyly syndrome (ClinVar).

How common is SMARCA2 p.Asp82= (c.246C>T) in the general population?

SMARCA2 p.Asp82= (c.246C>T) is rare (popmax 0.495%, eas) (gnomAD).

SMARCA2 p.Asp82=

c.246C>T · rs181403075 · VCV366195

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 7 submitters

gnomAD v4.1

Rare

rare (popmax 0.495%, eas)

Conditions

blepharophimosis-impaired intellectual development syndrome

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 0.24	GERP 0.019, phastCons 0.97
Overall
CADD	8.459	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.495% East Asian · 222/44,856 alleles

Filtering AF 0.442% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.421%

Overall 0.0175% 283/1,613,828 alleles · rare exomes 223/1,461,596 · genomes 60/152,232 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.495%	202
Remaining individualsnot grpmax-eligible	0.056%	1,786
South Asian	0.0242%	4,140
Admixed American	0.00667%	15,003

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.Asp82=
Coding: c.246C>T
MANE Select: NM_003070
dbSNP: rs181403075
Type: single nucleotide variant
Location: chr9:2032972 (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

blepharophimosis-impaired intellectual development syndrome — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: intellectual disability-sparse hair-brachydactyly syndrome

Similar variants

SMARCA2 p.Asp82Glu Uncertain significance ★ ⚠ 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-asp82 (accessed [today's date]).

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