Is SMARCC1 p.Pro545= (c.1635C>T) pathogenic?

SMARCC1 p.Pro545= (c.1635C>T) is classified Likely benign in SMARCC1 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2019-05-08). Ultra-rare (popmax 0.0146%, nfe); Associated with SMARCC1-related disorder.

What condition is associated with SMARCC1 p.Pro545= (c.1635C>T)?

SMARCC1 p.Pro545= (c.1635C>T) is associated with SMARCC1-related disorder (ClinVar).

How common is SMARCC1 p.Pro545= (c.1635C>T) in the general population?

SMARCC1 p.Pro545= (c.1635C>T) is ultra-rare (popmax 0.0146%, nfe) (gnomAD).

SMARCC1 p.Pro545=

c.1635C>T · rs370919273 · VCV3038269

Likely benign No assertion criteria

Classification

Likely benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.0146%, nfe)

Conditions

SMARCC1-related disorder

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -0.49	GERP -4.3, phastCons 0.003
Overall
CADD	6.223	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0146% European (non-Finnish) · 172/1,179,576 alleles

Filtering AF 0.0128% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0121%

Overall 0.0108% 174/1,613,322 alleles · ultra-rare exomes 167/1,461,206 · genomes 7/152,116 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.0146%	6,858
Remaining individualsnot grpmax-eligible	0.0032%	31,225

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: SMARCC1
Protein: p.Pro545=
Coding: c.1635C>T
MANE Select: NM_003074
dbSNP: rs370919273
Type: single nucleotide variant
Location: chr3:47676719 (GRCh38)
Gene constraint: LOEUF 0.369 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 66.98 · 5 PDB
Residue 545: a UniProt-annotated variant site (in hyc5); the swirm domain

Full SMARCC1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

SMARCC1-related disorder

Similar variants

SMARCC1 p.Arg923Gly Uncertain significance ★ ⚠ same condition
SMARCC1 p.Val535Ile Uncertain significance ★ ⚠ same condition
SMARCC1 c.2782-8G>C Likely benign same condition
SMARCC1 p.Ala747Thr Likely benign same condition
SMARCC1 p.Asn163Ser Benign same condition
SMARCC1 p.Asp214= Likely benign same condition
SMARCC1 p.Gln789= Likely benign same condition
SMARCC1 p.Ile1041= Likely benign 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/smarcc1-p-pro545 (accessed [today's date]).

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