Is SETD1A p.Ser430fs (c.1287dup) pathogenic?

SETD1A p.Ser430fs (c.1287dup) is classified Pathogenic in SETD1A (ClinVar, Single submitter, 1 submitter; last evaluated 2019-06-07). No gnomAD frequency available for this variant; Associated with epilepsy, early-onset, with or without developmental delay.

What condition is associated with SETD1A p.Ser430fs (c.1287dup)?

SETD1A p.Ser430fs (c.1287dup) is associated with epilepsy, early-onset, with or without developmental delay (ClinVar).

How common is SETD1A p.Ser430fs (c.1287dup) in the general population?

SETD1A p.Ser430fs (c.1287dup) is no gnomAD frequency available for this variant (gnomAD).

SETD1A p.Ser430fs

c.1287dup · rs2056118338 · VCV976774

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

epilepsy, early-onset, with or without developmental 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 19
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 6.6	GERP 1.6, 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: SETD1A
Protein: p.Ser430fs
Coding: c.1287dup
MANE Select: NM_014712
dbSNP: rs2056118338
Type: Duplication
Location: chr16:30965027 (GRCh38)
Gene constraint: LOEUF 0.279 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 49.20 · 4 PDB
Residue 430: a UniProt-annotated variant site (in nedsid); the 'disordered' region

Full SETD1A gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

epilepsy, early-onset, with or without developmental delay — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

SETD1A c.4582-2_4582-1del Pathogenic ★★ same condition
SETD1A p.Arg668Ter Pathogenic ★★ same condition
SETD1A p.Arg913Cys Likely pathogenic ★★ ⚠ same condition
SETD1A p.Arg990Ter Pathogenic/Likely pathogenic ★★ same condition
SETD1A p.Arg1392His Uncertain significance ★★ ⚠ same condition
SETD1A p.Arg276Trp Uncertain significance ★★ ⚠ same condition
SETD1A p.Arg311Pro Uncertain significance ★★ ⚠ same condition
SETD1A p.Arg461Cys Uncertain significance ★★ ⚠ 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/setd1a-p-ser430fs (accessed [today's date]).

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