Is SMARCA2 p.Arg1105Pro (c.3314G>C) pathogenic?

SMARCA2 p.Arg1105Pro (c.3314G>C) is classified Pathogenic/Likely pathogenic in SMARCA2 (ClinVar, Multiple submitters, 6 submitters; last evaluated 2023-10-31). AlphaMissense: likely pathogenic (0.9996); Absent from gnomAD v4.1; Associated with intellectual disability-sparse hair-brachydactyly syndrome.

What condition is associated with SMARCA2 p.Arg1105Pro (c.3314G>C)?

SMARCA2 p.Arg1105Pro (c.3314G>C) is associated with intellectual disability-sparse hair-brachydactyly syndrome (ClinVar).

How common is SMARCA2 p.Arg1105Pro (c.3314G>C) in the general population?

SMARCA2 p.Arg1105Pro (c.3314G>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about SMARCA2 p.Arg1105Pro (c.3314G>C)?

AlphaMissense predicts likely pathogenic (score 0.9996) — an in-silico prediction, not a clinical call.

SMARCA2 p.Arg1105Pro

c.3314G>C · rs281875197 · VCV68770

Pathogenic/Likely pathogenic Multiple submitters

Classification

Pathogenic/Likely pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 6 submitters

AlphaMissense

likely pathogenic

0.9996 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

intellectual disability-sparse hair-brachydactyly syndrome

Computational evidence

Protein change
AlphaMissense	0.9996	likely pathogenic ✓ concordant with ClinVar · top 4% in SMARCA2
REVEL	0.915	moderately pathogenic-leaning
SaProt	LLR -17.72	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 10	GERP 1.9, phastCons 1
Regional constraint	o/e 0.40	unconstrained · MANE · 23 kb · p 4.6e-21 · regional, not allelic
Overall
CADD	31.0	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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: SMARCA2
Protein: p.Arg1105Pro
Coding: c.3314G>C
MANE Select: NM_003070
dbSNP: rs281875197
Type: single nucleotide variant
Location: chr9:2110275 (GRCh38)
Gene constraint: LOEUF 0.317 · pLI 1.00 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 66.06 · 32 PDB
Residue 1105: an α-helix; the helicase c-terminal domain; a UniProt-annotated variant site (in ncbrs)

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.Arg1105Cys Pathogenic ★★ same residue
SMARCA2 p.Arg1105His Pathogenic ★★ same residue
SMARCA2 p.Arg1105Gly Pathogenic ★ same residue
SMARCA2 p.Arg1105Leu Likely pathogenic ★ same residue
SMARCA2 p.Ala1160Gly Pathogenic ★★ same condition
SMARCA2 p.Ala1201Val 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-arg1105pro (accessed [today's date]).

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