Is SET p.Lys141fs (c.420_421del) pathogenic?

SET p.Lys141fs (c.420421del) is classified Likely pathogenic in SET (ClinVar, No assertion criteria, 1 submitter). Associated with intellectual disability, autosomal dominant 58.

What condition is associated with SET p.Lys141fs (c.420_421del)?

SET p.Lys141fs (c.420_421del) is associated with intellectual disability, autosomal dominant 58 (ClinVar).

SET p.Lys141fs

c.420_421del · VCV4819996

Likely pathogenic No assertion criteria

Classification

Likely pathogenic

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

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 5 of 8
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 4.8	GERP 0.99, phastCons 1

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

Variant & gene context

Gene: SET
Protein: p.Lys141fs
Coding: c.420_421del
MANE Select: NM_003011
Type: Deletion
Location: chr9:128692909 (GRCh38)
Gene constraint: LOEUF 0.167 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 78.62 · 3 PDB
Residue 141: a β-strand; the 'earmuff domain' 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.Lys141Arg 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-lys141fs (accessed [today's date]).

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