Is ATL1 p.Pro545= (c.1635A>G) pathogenic?

ATL1 p.Pro545= (c.1635A>G) is classified Benign in ATL1 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2025-10-29). Rare (popmax 0.192%, eas); Associated with neuropathy, hereditary sensory, type 1D.

What condition is associated with ATL1 p.Pro545= (c.1635A>G)?

ATL1 p.Pro545= (c.1635A>G) is associated with neuropathy, hereditary sensory, type 1D, hereditary spastic paraplegia 3A (ClinVar).

How common is ATL1 p.Pro545= (c.1635A>G) in the general population?

ATL1 p.Pro545= (c.1635A>G) is rare (popmax 0.192%, eas) (gnomAD).

ATL1 p.Pro545=

Q: How is Hereditary sensory and autonomic neuropathy type 1 inherited?

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

c.1635A>G · rs191729308 · VCV883385

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

gnomAD v4.1

Rare

rare (popmax 0.192%, eas)

Conditions

neuropathy, hereditary sensory, type 1D

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 2.5	GERP 0.37, phastCons 1
Overall
CADD	8.169	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.192% East Asian · 86/44,798 alleles

Filtering AF 0.159% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.147%

Overall 0.00595% 96/1,613,618 alleles · rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.192%	521
Middle Eastern	0.0165%	6,056
Remaining individualsnot grpmax-eligible	0.0064%	15,621
South Asian	0.00439%	22,770
European (non-Finnish)	8.48e-05%	1,179,640

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.Pro545=
Coding: c.1635A>G
MANE Select: NM_015915
dbSNP: rs191729308
Type: single nucleotide variant
Location: chr14:50632297 (GRCh38)
Gene constraint: LOEUF 0.57 · pLI 0.36 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 86.49 · 14 PDB
Residue 545: the 'autoinhibitory domain' region

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

Disease context

neuropathy, hereditary sensory, type 1D — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: hereditary spastic paraplegia 3A

For Hereditary sensory and autonomic neuropathy type 1 (Orphanet):

Inheritance: Autosomal dominant
Onset: All ages

Similar variants

ATL1 p.Pro545Leu 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.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-pro545 (accessed [today's date]).

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