Is SMARCA2 p.Ala9Val (c.26C>T) pathogenic?

SMARCA2 p.Ala9Val (c.26C>T) is classified Uncertain significance in SMARCA2 (ClinVar, Single submitter, 2 submitters; last evaluated 2025-05-01). AlphaMissense: likely benign (0.1193); Ultra-rare (popmax 0.0188%, mid); Associated with intellectual disability-sparse hair-brachydactyly syndrome.

What condition is associated with SMARCA2 p.Ala9Val (c.26C>T)?

SMARCA2 p.Ala9Val (c.26C>T) is associated with intellectual disability-sparse hair-brachydactyly syndrome (ClinVar).

How common is SMARCA2 p.Ala9Val (c.26C>T) in the general population?

SMARCA2 p.Ala9Val (c.26C>T) is ultra-rare (popmax 0.0188%, mid) (gnomAD).

What do computational predictors say about SMARCA2 p.Ala9Val (c.26C>T)?

AlphaMissense predicts likely benign (score 0.1193) — an in-silico prediction, not a clinical call.

SMARCA2 p.Ala9Val

c.26C>T · rs773325366 · VCV3248528

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.1193 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0188%, mid)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

intellectual disability-sparse hair-brachydactyly syndrome

Computational evidence

Protein change
AlphaMissense	0.1193	likely benign
REVEL	0.246	benign-leaning
SaProt	LLR -6.91	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 3.3	GERP -1.2, phastCons 1
Regional constraint	o/e 1.11	unconstrained · MANE · 11 kb · p 0.08 · regional, not allelic
Overall
CADD	23.7	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0188% Middle Eastern · 1/5,310 alleles

Filtering AF 0.00725% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00557%

Overall 0.00148% 23/1,553,526 alleles · ultra-rare exomes 20/1,401,262 · genomes 3/152,264 · joint denominator

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0188%	5,310
South Asian	0.013%	7,698
Admixed American	0.0039%	25,625
Ashkenazi Jewishnot grpmax-eligible	0.00349%	28,676
European (non-Finnish)	0.000697%	143,552

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.Ala9Val
Coding: c.26C>T
MANE Select: NM_003070
dbSNP: rs773325366
Type: single nucleotide variant
Location: chr9:2029048 (GRCh38)
Gene constraint: LOEUF 0.317 · pLI 1.00 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 66.06 · 32 PDB
Residue 9: 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.Ala9= Likely benign ★ 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-ala9val (accessed [today's date]).

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