Is SET p.Ser148fs (c.442_443del) pathogenic?

SET p.Ser148fs (c.442443del) is classified Pathogenic in SET (ClinVar, Single submitter, 1 submitter; last evaluated 2024-12-20). Associated with intellectual disability, autosomal dominant 58.

What condition is associated with SET p.Ser148fs (c.442_443del)?

SET p.Ser148fs (c.442_443del) is associated with intellectual disability, autosomal dominant 58 (ClinVar).

SET p.Ser148fs

c.442_443del · VCV3392539

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

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 0.89	GERP -1.2, phastCons 1

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

Variant & gene context

Gene: SET
Protein: p.Ser148fs
Coding: c.442_443del
MANE Select: NM_003011
Type: Microsatellite
Location: chr9:128692928 (GRCh38)
Gene constraint: LOEUF 0.167 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 78.62 · 3 PDB
Residue 148: 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.Glu243fs Pathogenic ★ same condition
SET p.Ser140fs Pathogenic ★ same condition
SET p.Asp36del Uncertain significance ★ same condition
SET p.Thr85del Likely pathogenic same condition
SET c.663+5G>C Pathogenic ★★ same condition
SET p.Arg44fs Pathogenic/Likely pathogenic ★★ same condition
SET p.Gln69fs Pathogenic/Likely pathogenic ★★ same condition
SET p.His105Tyr 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/set-p-ser148fs (accessed [today's date]).

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