Is SMARCC2 p.Pro858= (c.2574A>G) pathogenic?

SMARCC2 p.Pro858= (c.2574A>G) is classified Likely benign in SMARCC2 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2019-05-07). Very rare (popmax 0.00364%, nfe); Associated with SMARCC2-related disorder.

What condition is associated with SMARCC2 p.Pro858= (c.2574A>G)?

SMARCC2 p.Pro858= (c.2574A>G) is associated with SMARCC2-related disorder (ClinVar).

How common is SMARCC2 p.Pro858= (c.2574A>G) in the general population?

SMARCC2 p.Pro858= (c.2574A>G) is very rare (popmax 0.00364%, nfe) (gnomAD).

SMARCC2 p.Pro858=

c.2574A>G · rs747112231 · VCV3037386

Likely benign No assertion criteria

Classification

Likely benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00364%, nfe)

Conditions

SMARCC2-related disorder

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 -1.8	GERP -2.8
Overall
CADD	6.258	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00364% European (non-Finnish) · 43/1,180,036 alleles

Filtering AF 0.00275% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00244%

Overall 0.00273% 44/1,614,052 alleles · very rare exomes 42/1,461,864 · genomes 2/152,188 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00364%	27,443
Remaining individualsnot grpmax-eligible	0.0016%	62,484

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.Pro858=
Coding: c.2574A>G
MANE Select: NM_001330288
dbSNP: rs747112231
Type: single nucleotide variant
Location: chr12:56169670 (GRCh38)
Gene constraint: LOEUF 0.167 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 64.89 · 9 PDB
Residue 858: a UniProt-annotated variant site (in css8)

Full SMARCC2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

SMARCC2-related disorder

Similar variants

SMARCC2 c.1926+1G>A Pathogenic/Likely pathogenic ★★ same condition
SMARCC2 p.Ala727Asp Likely pathogenic ★ same condition
SMARCC2 p.Leu640Pro Pathogenic ★ same condition
SMARCC2 p.Tyr257Ter Likely pathogenic ★ same condition
SMARCC2 p.Asn172Lys Uncertain significance ★ ⚠ same condition
SMARCC2 p.Glu147Asp Uncertain significance ★ ⚠ same condition
SMARCC2 p.His986Asn Uncertain significance ★ ⚠ same condition
SMARCC2 p.Ile1003Asn 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-pro858 (accessed [today's date]).

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