Is SETD1B p.Pro715fs (c.2144del) pathogenic?

SETD1B p.Pro715fs (c.2144del) is classified Likely pathogenic in SETD1B (ClinVar, Single submitter, 1 submitter; last evaluated 2025-11-13). Associated with intellectual developmental disorder with seizures and language delay.

What condition is associated with SETD1B p.Pro715fs (c.2144del)?

SETD1B p.Pro715fs (c.2144del) is associated with intellectual developmental disorder with seizures and language delay (ClinVar).

SETD1B p.Pro715fs

c.2144del · VCV4854993

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

Conditions

intellectual developmental disorder with seizures and language delay

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 7 of 17
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP -12	GERP -3.4
Region caveats
Repeat context	tandem	TGCCCCCACCGC simple repeat · ambiguous alignment · confidence, not pathogenicity

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

Variant & gene context

Gene: SETD1B
Protein: p.Pro715fs
Coding: c.2144del
MANE Select: NM_001353345
Type: Deletion
Location: chr12:121814355 (GRCh38)
Gene constraint: LOEUF 0.109 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 46.43 · 4 PDB
Residue 715: the 'disordered' region

Full SETD1B gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

intellectual developmental disorder with seizures and language delay — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

SETD1B p.Gly1392fs Pathogenic/Likely pathogenic ★★ same condition
SETD1B p.Arg1735fs Pathogenic ★ same condition
SETD1B p.Arg72fs Pathogenic ★ same condition
SETD1B p.Arg982fs Likely pathogenic ★ same condition
SETD1B p.Glu1199fs Likely pathogenic ★ same condition
SETD1B p.Glu94fs Likely pathogenic ★ same condition
SETD1B p.Gly362fs Likely pathogenic ★ same condition
SETD1B p.His720fs 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/setd1b-p-pro715fs (accessed [today's date]).

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