Is SETD1A p.Asp73fs (c.217_218del) pathogenic?

SETD1A p.Asp73fs (c.217218del) is classified Pathogenic in SETD1A (ClinVar, Single submitter, 1 submitter; last evaluated 2026-07-21). Associated with neurodevelopmental disorder with speech impairment and dysmorphic facies.

What condition is associated with SETD1A p.Asp73fs (c.217_218del)?

SETD1A p.Asp73fs (c.217_218del) is associated with neurodevelopmental disorder with speech impairment and dysmorphic facies (ClinVar).

SETD1A p.Asp73fs

c.217_218del · VCV4879629

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

Conditions

neurodevelopmental disorder with speech impairment and dysmorphic facies

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 3 of 19
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 4.8	GERP 2.1, phastCons 1

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

Variant & gene context

Gene: SETD1A
Protein: p.Asp73fs
Coding: c.217_218del
MANE Select: NM_014712
Type: Microsatellite
Location: chr16:30959154 (GRCh38)
Gene constraint: LOEUF 0.279 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 49.20 · 4 PDB
Residue 73: the 'interaction with wdr82' region; a UniProt-annotated variant site (in nedsid)

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

Disease context

neurodevelopmental disorder with speech impairment and dysmorphic facies — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

SETD1A p.Glu1368fs Uncertain significance ★★ same condition
SETD1A p.Glu1002fs Likely pathogenic ★ same condition
SETD1A p.Arg1402_Pro1403insArgArg Uncertain significance ★ same condition
SETD1A p.Glu455del Conflicting classifications of pathogenicity ★ same condition
SETD1A p.Ser1382_Ser1383del Uncertain significance ★ same condition
SETD1A c.4582-2_4582-1del Pathogenic ★★ same condition
SETD1A p.Arg1571Ter Pathogenic/Likely pathogenic ★★ same condition
SETD1A p.Arg176Ter Pathogenic/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/setd1a-p-asp73fs (accessed [today's date]).

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