Is ATL1 p.Pro384= (c.1152A>G) pathogenic?

ATL1 p.Pro384= (c.1152A>G) is classified Conflicting classifications of pathogenicity in ATL1 (ClinVar, Conflicting submitters, 4 submitters; last evaluated 2025-01-12). Ultra-rare (popmax 0.0506%, afr); Associated with hereditary spastic paraplegia 3A.

What condition is associated with ATL1 p.Pro384= (c.1152A>G)?

ATL1 p.Pro384= (c.1152A>G) is associated with hereditary spastic paraplegia 3A (ClinVar).

How common is ATL1 p.Pro384= (c.1152A>G) in the general population?

ATL1 p.Pro384= (c.1152A>G) is ultra-rare (popmax 0.0506%, afr) (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.Pro384=

c.1152A>G · rs377127492 · VCV313304

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 4 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0506%, afr)

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 -0.46	GERP -3.4, phastCons 0.12
Overall
CADD	5.99	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0506% African / African-American · 38/75,050 alleles

Filtering AF 0.0379% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0334%

Overall 0.00273% 44/1,614,214 alleles · ultra-rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0506%	1,975
Remaining individualsnot grpmax-eligible	0.0048%	20,837
Admixed American	0.00333%	30,015
European (non-Finnish)	8.47e-05%	1,180,027

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.Pro384=
Coding: c.1152A>G
MANE Select: NM_015915
dbSNP: rs377127492
Type: single nucleotide variant
Location: chr14:50628063 (GRCh38)
Gene constraint: LOEUF 0.57 · pLI 0.36 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 86.49 · 14 PDB
Residue 384: an α-helix; 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.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
ATL1 p.Gly409Cys 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-pro384 (accessed [today's date]).

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