Is SMARCC2 p.Ile461= (c.1383C>T) pathogenic?

SMARCC2 p.Ile461= (c.1383C>T) is classified Likely benign in SMARCC2 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-01-28). Very rare (popmax 0.00167%, amr); Associated with Inborn genetic diseases.

What condition is associated with SMARCC2 p.Ile461= (c.1383C>T)?

SMARCC2 p.Ile461= (c.1383C>T) is associated with Inborn genetic diseases (ClinVar).

How common is SMARCC2 p.Ile461= (c.1383C>T) in the general population?

SMARCC2 p.Ile461= (c.1383C>T) is very rare (popmax 0.00167%, amr) (gnomAD).

SMARCC2 p.Ile461=

c.1383C>T · VCV3798978

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00167%, amr)

Conditions

Inborn genetic diseases

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 3.5	GERP 0.81, phastCons 1
Overall
CADD	14.96	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00167% Admixed American · 1/59,748 alleles

Overall 0.000126% 2/1,585,966 alleles · very rare exomes 2/1,433,762 · genomes 0/152,204 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00167%	59,748
European (non-Finnish)	8.66e-05%	1,154,720

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: SMARCC2
Protein: p.Ile461=
Coding: c.1383C>T
MANE Select: NM_001330288
Type: single nucleotide variant
Location: chr12:56174764 (GRCh38)
Gene constraint: LOEUF 0.167 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 64.89 · 9 PDB
Residue 461: a UniProt-annotated variant site (in css8); the swirm domain; an α-helix

Full SMARCC2 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

Similar variants

SMARCC2 p.Gln1054Ter Pathogenic ★★ same condition
SMARCC2 p.Ala1198Thr Uncertain significance ★★ ⚠ same condition
SMARCC2 p.Arg288Gln Uncertain significance ★★ ⚠ same condition
SMARCC2 p.Asn351Ser Uncertain significance ★★ ⚠ same condition
SMARCC2 p.Gln1043His Uncertain significance ★★ ⚠ same condition
SMARCC2 p.Ile159Val Uncertain significance ★★ ⚠ same condition
SMARCC2 p.Pro1121Ser Uncertain significance ★★ ⚠ same condition
SMARCC2 p.Pro323Ser Uncertain significance ★★ ⚠ 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/smarcc2-p-ile461 (accessed [today's date]).

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