Is SMARCA2 p.Pro11Ser (c.31C>T) pathogenic?

SMARCA2 p.Pro11Ser (c.31C>T) is classified Benign/Likely benign in SMARCA2 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2025-12-15). AlphaMissense: likely benign (0.0913); Ultra-rare (popmax 0.0833%, afr); Associated with Inborn genetic diseases.

How common is SMARCA2 p.Pro11Ser (c.31C>T) in the general population?

SMARCA2 p.Pro11Ser (c.31C>T) is ultra-rare (popmax 0.0833%, afr) (gnomAD).

What do computational predictors say about SMARCA2 p.Pro11Ser (c.31C>T)?

AlphaMissense predicts likely benign (score 0.0913) — an in-silico prediction, not a clinical call.

SMARCA2 p.Pro11Ser

Q: What condition is associated with SMARCA2 p.Pro11Ser (c.31C>T)?

SMARCA2 p.Pro11Ser (c.31C>T) is associated with Inborn genetic diseases, intellectual disability-sparse hair-brachydactyly syndrome, blepharophimosis-impaired intellectual development syndrome (ClinVar).

c.31C>T · rs145516397 · VCV2174807

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

AlphaMissense

likely benign

0.0913 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0833%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.0913	likely benign
REVEL	0.281	benign-leaning
SaProt	LLR -6.92	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 7.7	GERP 2.7, phastCons 1
Regional constraint	o/e 1.11	unconstrained · MANE · 11 kb · p 0.08 · regional, not allelic
Overall
CADD	21.0	PHRED · no single calibrated threshold — expert panels disagree

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0833% African / African-American · 61/73,272 alleles

Filtering AF 0.0665% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0604%

Overall 0.00431% 67/1,555,250 alleles · ultra-rare exomes 38/1,402,874 · genomes 29/152,376 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0833%	1,201
Remaining individualsnot grpmax-eligible	0.00664%	15,057
Admixed American	0.00387%	25,814

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.Pro11Ser
Coding: c.31C>T
MANE Select: NM_003070
dbSNP: rs145516397
Type: single nucleotide variant
Location: chr9:2029053 (GRCh38)
Gene constraint: LOEUF 0.317 · pLI 1.00 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 66.06 · 32 PDB
Residue 11: the 'disordered' region

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 blepharophimosis-impaired intellectual development syndrome

Similar variants

SMARCA2 p.Pro11Thr Uncertain significance ★ ⚠ same residue
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

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-pro11ser (accessed [today's date]).

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