Is SET p.Glu261del (c.783_785del) pathogenic?

SET p.Glu261del (c.783785del) is classified Uncertain significance in SET (ClinVar, Single submitter, 1 submitter). Very rare (popmax 0.00231%, eas); Associated with intellectual disability, autosomal dominant 58.

What condition is associated with SET p.Glu261del (c.783_785del)?

SET p.Glu261del (c.783_785del) is associated with intellectual disability, autosomal dominant 58 (ClinVar).

How common is SET p.Glu261del (c.783_785del) in the general population?

SET p.Glu261del (c.783_785del) is very rare (popmax 0.00231%, eas) (gnomAD).

SET p.Glu261del

c.783_785del · rs1458424469 · VCV2585464

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00231%, eas)

Conditions

intellectual disability, autosomal dominant 58

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP -0.22	GERP -1.3, phastCons 0.65
Overall
CADD	21.8	PHRED · no single calibrated threshold — expert panels disagree
Region caveats
Repeat context	tandem	GA-rich low complexity · ambiguous alignment · confidence, not pathogenicity

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00231% East Asian · 1/43,358 alleles

Filtering AF 0.000841% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00068%

Overall 0.00117% 18/1,538,514 alleles · very rare exomes 17/1,387,252 · genomes 1/151,262 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00231%	43,358
European (non-Finnish)	0.00142%	70,413
South Asian	0.00117%	85,782

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: SET
Protein: p.Glu261del
Coding: c.783_785del
MANE Select: NM_003011
dbSNP: rs1458424469
Type: Deletion
Location: chr9:128694013 (GRCh38)
Gene constraint: LOEUF 0.167 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 78.62 · 3 PDB
Residue 261: a UniProt-annotated variant site (in mrd58); the 'disordered' region

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

Disease context

intellectual disability, autosomal dominant 58 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

SET p.Glu261Asp Uncertain significance ★★ ⚠ same residue
SET p.Arg44fs Pathogenic/Likely pathogenic ★★ same condition
SET c.493-3_504del Pathogenic ★ same condition
SET p.Asp36fs Pathogenic ★ same condition
SET p.Glu114fs Likely pathogenic ★ same condition
SET p.Glu73fs Likely pathogenic ★ same condition
SET p.His34_Ile35insTer Likely pathogenic ★ same condition
SET p.Lys26fs 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/set-p-glu261del (accessed [today's date]).

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