Is SET p.Ser140fs (c.418_419del) pathogenic?

SET p.Ser140fs (c.418419del) is classified Pathogenic in SET (ClinVar, Single submitter, 1 submitter; last evaluated 2018-11-21). No gnomAD frequency available for this variant; Associated with intellectual disability, autosomal dominant 58.

What condition is associated with SET p.Ser140fs (c.418_419del)?

SET p.Ser140fs (c.418_419del) is associated with intellectual disability, autosomal dominant 58 (ClinVar).

How common is SET p.Ser140fs (c.418_419del) in the general population?

SET p.Ser140fs (c.418_419del) is no gnomAD frequency available for this variant (gnomAD).

SET p.Ser140fs

c.418_419del · rs1589460606 · VCV807681

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

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	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 5	GERP 1, 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.Ser140fs
Coding: c.418_419del
MANE Select: NM_003011
dbSNP: rs1589460606
Type: Microsatellite
Location: chr9:128692903 (GRCh38)
Gene constraint: LOEUF 0.167 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 78.62 · 3 PDB
Residue 140: 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.Glu243fs Pathogenic ★ same condition
SET p.Ser148fs 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-ser140fs (accessed [today's date]).

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