Is SETD1B p.Arg511fs (c.1529dup) pathogenic?

SETD1B p.Arg511fs (c.1529dup) is classified Pathogenic in SETD1B (ClinVar, Single submitter, 1 submitter; last evaluated 2025-10-20). Associated with intellectual developmental disorder with seizures and language delay.

What condition is associated with SETD1B p.Arg511fs (c.1529dup)?

SETD1B p.Arg511fs (c.1529dup) is associated with intellectual developmental disorder with seizures and language delay (ClinVar).

SETD1B p.Arg511fs

c.1529dup · VCV4850206

Pathogenic Single submitter

Classification

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 6 of 17
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 7.5	GERP 1.9, phastCons 1

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

Variant & gene context

Gene: SETD1B
Protein: p.Arg511fs
Coding: c.1529dup
MANE Select: NM_001353345
Type: Duplication
Location: chr12:121810473 (GRCh38)
Gene constraint: LOEUF 0.109 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 46.43 · 4 PDB
Residue 511: 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.Asp458fs Pathogenic ★★ same condition
SETD1B p.His8fs Pathogenic ★★ same condition
SETD1B p.Ala1776fs Pathogenic ★ same condition
SETD1B p.Asn1709fs Likely pathogenic ★ same condition
SETD1B p.Asp1736fs Likely pathogenic ★ same condition
SETD1B p.Gln200fs Pathogenic ★ same condition
SETD1B p.Glu412fs Pathogenic ★ same condition
SETD1B p.Ser1880fs 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-arg511fs (accessed [today's date]).

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