Is SMARCC2 p.Pro1073= (c.3219C>A) pathogenic?

SMARCC2 p.Pro1073= (c.3219C>A) is classified Likely benign in SMARCC2 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-11-27). Very rare (popmax 0.00734%, amr); Associated with Inborn genetic diseases.

What condition is associated with SMARCC2 p.Pro1073= (c.3219C>A)?

SMARCC2 p.Pro1073= (c.3219C>A) is associated with Inborn genetic diseases (ClinVar).

How common is SMARCC2 p.Pro1073= (c.3219C>A) in the general population?

SMARCC2 p.Pro1073= (c.3219C>A) is very rare (popmax 0.00734%, amr) (gnomAD).

SMARCC2 p.Pro1073=

c.3219C>A · VCV3446114

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00734%, amr)

Conditions

Inborn genetic diseases

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 10	GERP 1.2, phastCons 1
Overall
CADD	8.719	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00734% Admixed American · 3/40,868 alleles

Filtering AF 0.00195% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00114%

Overall 0.00241% 36/1,496,180 alleles · very rare exomes 31/1,343,938 · genomes 5/152,242 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00734%	13,623
Remaining individualsnot grpmax-eligible	0.00525%	19,039
East Asian	0.00476%	21,014
South Asian	0.00416%	24,055
African / African-American	0.00282%	35,426
European (non-Finnish)	0.00204%	48,975

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.Pro1073=
Coding: c.3219C>A
MANE Select: NM_001330288
Type: single nucleotide variant
Location: chr12:56165331 (GRCh38)
Gene constraint: LOEUF 0.167 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 64.89 · 9 PDB
Residue 1073: the 'disordered' region; a UniProt-annotated variant site (in css8)

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.Pro1073His Conflicting classifications of pathogenicity ★ ⚠ same residue
SMARCC2 p.Pro1073Ser Uncertain significance ★ ⚠ same residue
SMARCC2 p.Pro1073Leu Likely benign ★ same residue
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

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-pro1073 (accessed [today's date]).

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