Is ATL1 p.Pro344fs (c.1030_1040del) pathogenic?

ATL1 p.Pro344fs (c.10301040del) is classified Pathogenic in ATL1 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-01-06). Absent from gnomAD; Associated with hereditary spastic paraplegia 3A.

What condition is associated with ATL1 p.Pro344fs (c.1030_1040del)?

ATL1 p.Pro344fs (c.1030_1040del) is associated with hereditary spastic paraplegia 3A (ClinVar).

How common is ATL1 p.Pro344fs (c.1030_1040del) in the general population?

ATL1 p.Pro344fs (c.1030_1040del) is absent from gnomAD (gnomAD).

How is Autosomal dominant spastic paraplegia type 3 inherited?

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

ATL1 p.Pro344fs

c.1030_1040del · rs2504560480 · VCV2826561

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

hereditary spastic paraplegia 3A

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function
NMD	predicted	premature termination codon in exon 10 of 14
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 1.7	GERP 0.54, 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: ATL1
Protein: p.Pro344fs
Coding: c.1030_1040del
MANE Select: NM_015915
dbSNP: rs2504560480
Type: Deletion
Location: chr14:50621879 (GRCh38)
Gene constraint: LOEUF 0.57 · pLI 0.36 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 86.49 · 14 PDB
Residue 344: an α-helix

Full ATL1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

hereditary spastic paraplegia 3A — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Autosomal dominant spastic paraplegia type 3 (Orphanet):

Inheritance: Autosomal dominant
Onset: Adult, Childhood
Prevalence: 1-9 / 1 000 000 (Portugal)

Similar variants

ATL1 p.Pro344Thr Uncertain significance ★ ⚠ same residue
ATL1 p.Pro344Ser Uncertain significance ⚠ same residue
ATL1 p.Asn436del Pathogenic/Likely pathogenic ★★ same condition
ATL1 c.723+3_723+19del Uncertain significance ★★ same condition
ATL1 c.1552-24_1552-20del Benign ★★ same condition
ATL1 p.Arg403fs Pathogenic ★ same condition
ATL1 p.Gln174fs Pathogenic ★ same condition
ATL1 p.Gly504fs 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/atl1-p-pro344fs (accessed [today's date]).

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