Is SMARCE1 p.Pro89= (c.267T>C) pathogenic?

SMARCE1 p.Pro89= (c.267T>C) is classified Likely benign in SMARCE1 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-07-17). Very rare (popmax 0.00534%, afr); Associated with hereditary neoplastic syndrome.

What condition is associated with SMARCE1 p.Pro89= (c.267T>C)?

SMARCE1 p.Pro89= (c.267T>C) is associated with hereditary neoplastic syndrome, familial meningioma (ClinVar).

How common is SMARCE1 p.Pro89= (c.267T>C) in the general population?

SMARCE1 p.Pro89= (c.267T>C) is very rare (popmax 0.00534%, afr) (gnomAD).

SMARCE1 p.Pro89=

c.267T>C · rs1460253575 · VCV1110159

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

very rare (popmax 0.00534%, afr)

Conditions

hereditary neoplastic syndrome

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 4.1	GERP -3, phastCons 1
Overall
CADD	12.19	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00534% African / African-American · 4/74,972 alleles

Filtering AF 0.00175% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00104%

Overall 0.00031% 5/1,612,314 alleles · very rare exomes 2/1,459,982 · genomes 3/152,332 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00534%	18,743
Remaining individualsnot grpmax-eligible	0.0016%	62,422

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: SMARCE1
Protein: p.Pro89=
Coding: c.267T>C
MANE Select: NM_003079
dbSNP: rs1460253575
Type: single nucleotide variant
Location: chr17:40636497 (GRCh38)
Gene constraint: LOEUF 0.318 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 70.72 · 8 PDB
Residue 89: a DNA-binding region

Full SMARCE1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

hereditary neoplastic syndrome — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: familial meningioma

Similar variants

SMARCE1 p.Pro89Thr Uncertain significance ★ ⚠ same residue
SMARCE1 p.Pro89Leu Uncertain significance ★ ⚠ same residue
SMARCE1 p.Arg105Gln Pathogenic/Likely pathogenic ★★ same condition
SMARCE1 p.Arg158Ter Pathogenic ★★ same condition
SMARCE1 p.Arg239Ter Pathogenic ★★ same condition
SMARCE1 p.Arg251Ter Pathogenic/Likely pathogenic ★★ same condition
SMARCE1 p.Gln225Ter Pathogenic ★★ same condition
SMARCE1 p.Glu110Ter Pathogenic ★★ 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/smarce1-p-pro89 (accessed [today's date]).

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