Is SMARCE1 p.Pro320fs (c.959del) pathogenic?

SMARCE1 p.Pro320fs (c.959del) is classified Likely pathogenic in SMARCE1 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-07-29). No gnomAD frequency available for this variant; Associated with hereditary neoplastic syndrome.

What condition is associated with SMARCE1 p.Pro320fs (c.959del)?

SMARCE1 p.Pro320fs (c.959del) is associated with hereditary neoplastic syndrome (ClinVar).

How common is SMARCE1 p.Pro320fs (c.959del) in the general population?

SMARCE1 p.Pro320fs (c.959del) is no gnomAD frequency available for this variant (gnomAD).

SMARCE1 p.Pro320fs

c.959del · rs2508595907 · VCV2626165

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Not reported

no gnomAD frequency available for this variant

Conditions

hereditary neoplastic syndrome

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function in a haploinsufficient gene (ClinGen)
NMD	predicted	premature termination codon in exon 10 of 11
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP -5.5	GERP -4.2

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

dbSNP / gnomAD

No gnomAD frequency available for this variant. This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: SMARCE1
Protein: p.Pro320fs
Coding: c.959del
MANE Select: NM_003079
dbSNP: rs2508595907
Type: Deletion
Location: chr17:40630782 (GRCh38)
Gene constraint: LOEUF 0.318 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 70.72 · 8 PDB
Residue 320: the 'disordered' 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

Similar variants

SMARCE1 p.Pro320Ser Uncertain significance ★★ ⚠ same residue
SMARCE1 p.Pro320Leu Conflicting classifications of pathogenicity ★ ⚠ same residue
SMARCE1 p.Gly185fs Pathogenic/Likely pathogenic ★★ same condition
SMARCE1 p.Glu254del Uncertain significance ★★ same condition
SMARCE1 p.Glu330_Asp334del Uncertain significance ★★ same condition
SMARCE1 p.Lys305del Uncertain significance ★★ same condition
SMARCE1 p.Pro364del Uncertain significance ★★ same condition
SMARCE1 c.816+1del Likely 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-pro320fs (accessed [today's date]).

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