Is SET p.Glu47Ter (c.138dup) pathogenic?

SET p.Glu47Ter (c.138dup) is classified Likely pathogenic in SET (ClinVar, Single submitter, 1 submitter; last evaluated 2023-02-01). Absent from gnomAD; Associated with intellectual disability, autosomal dominant 58.

What condition is associated with SET p.Glu47Ter (c.138dup)?

SET p.Glu47Ter (c.138dup) is associated with intellectual disability, autosomal dominant 58 (ClinVar).

How common is SET p.Glu47Ter (c.138dup) in the general population?

SET p.Glu47Ter (c.138dup) is absent from gnomAD (gnomAD).

SET p.Glu47Ter

c.138dup · rs2523226839 · VCV2505260

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

nonsense (stop-gain)

predicted LoF

gnomAD v4.1

Not reported

no gnomAD frequency available for this variant

Conditions

intellectual disability, autosomal dominant 58

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	nonsense (stop-gain)	predicted loss-of-function in a haploinsufficient gene (ClinGen)
NMD	predicted	premature termination codon in exon 3 of 8
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 11	GERP 2, phastCons 1

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: SET
Protein: p.Glu47Ter
Coding: c.138dup
MANE Select: NM_003011
dbSNP: rs2523226839
Type: Duplication
Location: chr9:128691863 (GRCh38)
Gene constraint: LOEUF 0.167 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 78.62 · 3 PDB
Residue 47: an α-helix; the 'dimerization' 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.Gln69fs Pathogenic/Likely pathogenic ★★ same condition
SET p.Asn215fs Pathogenic ★ same condition
SET p.Gln218fs Pathogenic same condition
SET c.663+5G>C Pathogenic ★★ same condition
SET p.Arg44fs Pathogenic/Likely pathogenic ★★ same condition
SET p.His105Tyr Likely pathogenic ★★ same condition
SET p.Asp224Asn Uncertain significance ★★ ⚠ same condition
SET p.Asp260Glu 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/set-p-glu47ter (accessed [today's date]).

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