Is ANK3 p.Pro3678fs (c.11033del) pathogenic?

ANK3 p.Pro3678fs (c.11033del) is classified Pathogenic in ANK3 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2022-04-08). Absent from gnomAD; Associated with intellectual disability-hypotonia-spasticity-sleep disorder syndrome.

What condition is associated with ANK3 p.Pro3678fs (c.11033del)?

ANK3 p.Pro3678fs (c.11033del) is associated with intellectual disability-hypotonia-spasticity-sleep disorder syndrome (ClinVar).

How common is ANK3 p.Pro3678fs (c.11033del) in the general population?

ANK3 p.Pro3678fs (c.11033del) is absent from gnomAD (gnomAD).

ANK3 p.Pro3678fs

Q: How is ANK3-related intellectual disability-sleep disturbance syndrome inherited?

Typically Autosomal recessive (Orphanet). A genetic counselor can assess individual risk for a family.

c.11033del · rs2082373823 · VCV918004

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 disability-hypotonia-spasticity-sleep disorder syndrome

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 LoF-intolerant gene
NMD	predicted	premature termination codon in exon 37 of 44
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 2.9	GERP 3, phastCons 0.87

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: ANK3
Protein: p.Pro3678fs
Coding: c.11033del
MANE Select: NM_020987
dbSNP: rs2082373823
Type: Deletion
Location: chr10:60069848 (GRCh38)
Gene constraint: LOEUF 0.16 · pLI 1.00 (gnomAD)
Residue 3678: the 'disordered' region

Full ANK3 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

intellectual disability-hypotonia-spasticity-sleep disorder syndrome — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For ANK3-related intellectual disability-sleep disturbance syndrome (Orphanet):

Inheritance: Autosomal recessive
Onset: Childhood

Similar variants

ANK3 p.Arg1456fs Pathogenic/Likely pathogenic ★★ same condition
ANK3 p.Ala1197fs Pathogenic ★ same condition
ANK3 p.Glu3465fs Uncertain significance ★ same condition
ANK3 p.Thr3666fs Pathogenic same condition
ANK3 p.Pro3678Leu Uncertain significance ⚠ same residue
ANK3 p.Ala1630Val Uncertain significance ★★ ⚠ same condition
ANK3 p.Ala2023Thr Uncertain significance ★★ ⚠ same condition
ANK3 p.Ala628Thr 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/ank3-p-pro3678fs (accessed [today's date]).

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