Is SMARCC1 p.Ser45= (c.135C>T) pathogenic?

SMARCC1 p.Ser45= (c.135C>T) is classified Likely benign in SMARCC1 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2019-02-26). Rare (popmax 0.465%, eas); Associated with SMARCC1-related disorder.

What condition is associated with SMARCC1 p.Ser45= (c.135C>T)?

SMARCC1 p.Ser45= (c.135C>T) is associated with SMARCC1-related disorder (ClinVar).

How common is SMARCC1 p.Ser45= (c.135C>T) in the general population?

SMARCC1 p.Ser45= (c.135C>T) is rare (popmax 0.465%, eas) (gnomAD).

SMARCC1 p.Ser45=

c.135C>T · rs146832470 · VCV3041060

Likely benign No assertion criteria

Classification

Likely benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

rare (popmax 0.465%, eas)

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 5	GERP 0.53, phastCons 1
Overall
CADD	14.19	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.465% East Asian · 174/37,436 alleles

Filtering AF 0.408% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.387%

Overall 0.0243% 379/1,558,546 alleles · rare exomes 333/1,406,632 · genomes 46/151,914 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.465%	215
Admixed American	0.363%	275
Remaining individualsnot grpmax-eligible	0.01%	9,976
African / African-American	0.00568%	17,616
European (non-Finnish)	0.000692%	144,557

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.Ser45=
Coding: c.135C>T
MANE Select: NM_003074
dbSNP: rs146832470
Type: single nucleotide variant
Location: chr3:47781663 (GRCh38)
Gene constraint: LOEUF 0.369 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 66.98 · 5 PDB
Residue 45: the marr-like domain; the 'marr-like, brct and chromo domains module' region

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

Disease context

SMARCC1-related disorder

Similar variants

SMARCC1 p.Ser45Arg Uncertain significance ★ ⚠ same residue
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

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-ser45 (accessed [today's date]).

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