Is SMARCA2 p.Pro108= (c.324T>A) pathogenic?

SMARCA2 p.Pro108= (c.324T>A) is classified Conflicting classifications of pathogenicity in SMARCA2 (ClinVar, Conflicting submitters, 2 submitters; last evaluated 2026-01-05). Very rare (popmax 0.00814%, nfe); Associated with intellectual disability-sparse hair-brachydactyly syndrome.

What condition is associated with SMARCA2 p.Pro108= (c.324T>A)?

SMARCA2 p.Pro108= (c.324T>A) is associated with intellectual disability-sparse hair-brachydactyly syndrome (ClinVar).

How common is SMARCA2 p.Pro108= (c.324T>A) in the general population?

SMARCA2 p.Pro108= (c.324T>A) is very rare (popmax 0.00814%, nfe) (gnomAD).

SMARCA2 p.Pro108=

c.324T>A · rs150630640 · VCV914395

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

very rare (popmax 0.00814%, nfe)

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	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP -0.77	GERP -4.2, phastCons 0.016
Overall
CADD	8.71	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00814% European (non-Finnish) · 96/1,179,946 alleles

Filtering AF 0.00681% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00633%

Overall 0.00632% 102/1,613,916 alleles · very rare exomes 93/1,461,750 · genomes 9/152,166 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00814%	12,291
African / African-American	0.004%	24,971
Remaining individualsnot grpmax-eligible	0.0032%	31,238
Finnishnot grpmax-eligible	0.00156%	64,028

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.Pro108=
Coding: c.324T>A
MANE Select: NM_003070
dbSNP: rs150630640
Type: single nucleotide variant
Location: chr9:2033050 (GRCh38)
Gene constraint: LOEUF 0.317 · pLI 1.00 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 66.06 · 32 PDB
Residue 108: 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-pro108 (accessed [today's date]).

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