Is ATL1 p.Arg415= (c.1245G>A) pathogenic?

ATL1 p.Arg415= (c.1245G>A) is classified Likely benign in ATL1 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-10-15). Very rare (popmax 0.00203%, nfe); Associated with hereditary spastic paraplegia 3A.

What condition is associated with ATL1 p.Arg415= (c.1245G>A)?

ATL1 p.Arg415= (c.1245G>A) is associated with hereditary spastic paraplegia 3A (ClinVar).

How common is ATL1 p.Arg415= (c.1245G>A) in the general population?

ATL1 p.Arg415= (c.1245G>A) is very rare (popmax 0.00203%, nfe) (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.Arg415=

c.1245G>A · rs979353252 · VCV1546587

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00203%, nfe)

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 0.24	GERP 0.097, phastCons 0.92
Overall
CADD	6.845	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00203% European (non-Finnish) · 24/1,180,042 alleles

Filtering AF 0.00138% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00116%

Overall 0.00149% 24/1,614,050 alleles · very rare exomes 21/1,461,892 · genomes 3/152,158 · joint denominator

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.Arg415=
Coding: c.1245G>A
MANE Select: NM_015915
dbSNP: rs979353252
Type: single nucleotide variant
Location: chr14:50628156 (GRCh38)
Gene constraint: LOEUF 0.57 · pLI 0.36 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 86.49 · 14 PDB
Residue 415: an α-helix; a UniProt-annotated variant site (in spg3); the '3hb (three-helix bundle) domain' 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.Arg415Trp Pathogenic/Likely pathogenic ★★ ⚠ same residue
ATL1 p.Arg415Gln Conflicting classifications of pathogenicity ★ ⚠ same residue
ATL1 p.Arg415Pro Uncertain significance ★ ⚠ 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.Arg416Cys 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-arg415 (accessed [today's date]).

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