Is SET p.Gln69fs (c.204dup) pathogenic?

SET p.Gln69fs (c.204dup) is classified Pathogenic/Likely pathogenic in SET (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-10-12). Associated with intellectual disability, autosomal dominant 58.

What condition is associated with SET p.Gln69fs (c.204dup)?

SET p.Gln69fs (c.204dup) is associated with intellectual disability, autosomal dominant 58 (ClinVar).

SET p.Gln69fs

c.204dup · VCV4076402

Pathogenic/Likely pathogenic Multiple submitters

Classification

Pathogenic/Likely pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

Conditions

intellectual disability, autosomal dominant 58

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 3 of 8
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP -0.52	GERP -0.039

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

Variant & gene context

Gene: SET
Protein: p.Gln69fs
Coding: c.204dup
MANE Select: NM_003011
Type: Duplication
Location: chr9:128691924 (GRCh38)
Gene constraint: LOEUF 0.167 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 78.62 · 3 PDB
Residue 69: 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.Asn215fs Pathogenic ★ same condition
SET p.Glu47Ter Likely 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-gln69fs (accessed [today's date]).

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