Is ATN1 p.Pro461fs (c.1380_1383del) pathogenic?

ATN1 p.Pro461fs (c.13801383del) is classified Uncertain significance in ATN1 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-09-10). Associated with congenital hypotonia, epilepsy, developmental delay, and digital anomalies.

What condition is associated with ATN1 p.Pro461fs (c.1380_1383del)?

ATN1 p.Pro461fs (c.1380_1383del) is associated with congenital hypotonia, epilepsy, developmental delay, and digital anomalies (ClinVar).

ATN1 p.Pro461fs

c.1380_1383del · VCV4278205

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

Conditions

congenital hypotonia, epilepsy, developmental delay, and digital anomalies

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 5 of 10
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 6.7	GERP -2.3, phastCons 1

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

Variant & gene context

Gene: ATN1
Protein: p.Pro461fs
Coding: c.1380_1383del
MANE Select: NM_001940
Type: Deletion
Location: chr12:6936647 (GRCh38)
Gene constraint: LOEUF 0.352 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 49.25
Residue 461: the 'disordered' region

Full ATN1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

congenital hypotonia, epilepsy, developmental delay, and digital anomalies — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

ATN1 p.Ile1057_His1060del Pathogenic ★★ same condition
ATN1 p.Asp144_Ser148del Uncertain significance ★ same condition
ATN1 p.1061LH[3] Pathogenic/Likely pathogenic ★★ same condition
ATN1 p.His1052Pro Pathogenic/Likely pathogenic ★★ same condition
ATN1 p.Ser1059Leu Pathogenic/Likely pathogenic ★★ same condition
ATN1 p.Thr871Ala Uncertain significance ★★ ⚠ same condition
ATN1 p.Gln489= Likely benign ★★ same condition
ATN1 p.Gln497_Gln502dup Benign/Likely benign ★★ 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/atn1-p-pro461fs (accessed [today's date]).

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