Is SETD1B p.Ile1925fs (c.5773_5776del) pathogenic?

SETD1B p.Ile1925fs (c.57735776del) is classified Pathogenic in SETD1B (ClinVar, No assertion criteria, 1 submitter; last evaluated 2020-09-03). No gnomAD frequency available for this variant; Associated with intellectual developmental disorder with seizures and language delay.

What condition is associated with SETD1B p.Ile1925fs (c.5773_5776del)?

SETD1B p.Ile1925fs (c.5773_5776del) is associated with intellectual developmental disorder with seizures and language delay (ClinVar).

How common is SETD1B p.Ile1925fs (c.5773_5776del) in the general population?

SETD1B p.Ile1925fs (c.5773_5776del) is no gnomAD frequency available for this variant (gnomAD).

SETD1B p.Ile1925fs

c.5773_5776del · rs1877023557 · VCV977478

Pathogenic No assertion criteria

Classification

Pathogenic

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Not reported

no gnomAD frequency available for this variant

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	escapes	premature termination codon in the last exon (17 of 17) — the truncated protein is likely expressed. PVS1 input, not an applied code
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 11	GERP -0.32, 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: SETD1B
Protein: p.Ile1925fs
Coding: c.5773_5776del
MANE Select: NM_001353345
dbSNP: rs1877023557
Type: Deletion
Location: chr12:121830109 (GRCh38)
Gene constraint: LOEUF 0.109 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 46.43 · 4 PDB
Residue 1925: the set domain; a UniProt-annotated variant site (in iddseld)

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-ile1925fs (accessed [today's date]).

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