Is ATL1 p.Ser15= (c.45G>A) pathogenic?

ATL1 p.Ser15= (c.45G>A) is classified Likely benign in ATL1 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2026-04-01). Rare (popmax 0.115%, mid); Associated with hereditary spastic paraplegia 3A.

What condition is associated with ATL1 p.Ser15= (c.45G>A)?

ATL1 p.Ser15= (c.45G>A) is associated with hereditary spastic paraplegia 3A (ClinVar).

How common is ATL1 p.Ser15= (c.45G>A) in the general population?

ATL1 p.Ser15= (c.45G>A) is rare (popmax 0.115%, mid) (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.Ser15=

c.45G>A · rs775540772 · VCV697332

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

gnomAD v4.1

Rare

rare (popmax 0.115%, mid)

Conditions

hereditary spastic paraplegia 3A

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 3.4	GERP -2.4, phastCons 1
Overall
CADD	11.77	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.115% Middle Eastern · 7/6,084 alleles

Filtering AF 0.054% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0383%

Overall 0.00601% 97/1,614,008 alleles · rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.115%	869
South Asian	0.0187%	5,358
Remaining individualsnot grpmax-eligible	0.0144%	6,942
Admixed American	0.0133%	7,500
African / African-American	0.00534%	18,725
European (non-Finnish)	0.00432%	23,138
East Asian	0.00223%	44,896

Rarity supports pathogenicity (ACMG PM2); frequency above a disease-specific BA1/BS1 threshold argues against it. A variant frequent in one ancestry group can be near-absent in others, so a single global figure can mislead.

Variant & gene context

Gene: ATL1
Protein: p.Ser15=
Coding: c.45G>A
MANE Select: NM_015915
dbSNP: rs775540772
Type: single nucleotide variant
Location: chr14:50587841 (GRCh38)
Gene constraint: LOEUF 0.57 · pLI 0.36 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 86.49 · 14 PDB
Residue 15: the 'n-terminal hypervariable region (hvr)' region; the 'disordered' region

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.Ser15Leu Conflicting classifications of pathogenicity ★ ⚠ same residue
ATL1 p.Arg217Gln Pathogenic/Likely pathogenic ★★ same condition
ATL1 p.Arg239Cys Pathogenic/Likely pathogenic ★★ same condition
ATL1 p.Arg239His Likely pathogenic ★★ same condition
ATL1 p.Arg403Pro Likely pathogenic ★★ same condition
ATL1 p.Arg415Trp Pathogenic/Likely pathogenic ★★ ⚠ same condition
ATL1 p.Arg416Cys Pathogenic/Likely pathogenic ★★ ⚠ same condition
ATL1 p.Arg495Trp 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/atl1-p-ser15 (accessed [today's date]).

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