Is SMARCC2 p.Pro1089Ser (c.3265C>T) pathogenic?

SMARCC2 p.Pro1089Ser (c.3265C>T) is classified Likely benign in SMARCC2 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2026-03-01). AlphaMissense: likely benign (0.0565); Low-frequency (popmax 1.01%, afr); Associated with Inborn genetic diseases.

What condition is associated with SMARCC2 p.Pro1089Ser (c.3265C>T)?

SMARCC2 p.Pro1089Ser (c.3265C>T) is associated with Inborn genetic diseases (ClinVar).

How common is SMARCC2 p.Pro1089Ser (c.3265C>T) in the general population?

SMARCC2 p.Pro1089Ser (c.3265C>T) is low-frequency (popmax 1.01%, afr) (gnomAD).

What do computational predictors say about SMARCC2 p.Pro1089Ser (c.3265C>T)?

AlphaMissense predicts likely benign (score 0.0565) — an in-silico prediction, not a clinical call.

SMARCC2 p.Pro1089Ser

c.3265C>T · rs76701112 · VCV3234282

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

AlphaMissense

likely benign

0.0565 · ACMG-weighted

gnomAD v4.1

Rare

low-frequency (popmax 1.01%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.0565	likely benign
REVEL	0.069	moderately benign-leaning
SaProt	LLR -6.64	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 1.6, phastCons 1
Regional constraint	o/e 0.89	unconstrained · MANE · 1,903 bp · p 0.032 · regional, not allelic
Overall
CADD	21.5	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

⚠ Isoform check: AlphaMissense numbered on a different transcript (AM P1058S vs ClinVar P1089S) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 1.01% African / African-American · 760/75,012 alleles

Filtering AF 0.953% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.93%

Overall 0.0725% 1,168/1,611,364 alleles · low-frequency

Ancestry group	Frequency	1 in
African / African-Americangrpmax	1.01%	99
Ashkenazi Jewishnot grpmax-eligible	0.573%	175
Admixed American	0.15%	668
Remaining individualsnot grpmax-eligible	0.138%	726
Middle Eastern	0.0167%	5,990
European (non-Finnish)	0.00501%	19,980
South Asian	0.00331%	30,215
Finnishnot grpmax-eligible	0.00157%	63,838

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.Pro1089Ser
Coding: c.3265C>T
MANE Select: NM_001330288
dbSNP: rs76701112
Type: single nucleotide variant
Location: chr12:56164699 (GRCh38)
Gene constraint: LOEUF 0.167 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 64.89 · 9 PDB
Residue 1089: 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.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-pro1089ser (accessed [today's date]).

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