Is ATL3 p.Ala507= (c.1521C>T) pathogenic?

ATL3 p.Ala507= (c.1521C>T) is classified Likely benign in ATL3 (ClinVar, Multiple submitters, 6 submitters; last evaluated 2026-01-12). Rare (popmax 0.142%, nfe); Associated with neuropathy, hereditary sensory, type 1F.

What condition is associated with ATL3 p.Ala507= (c.1521C>T)?

ATL3 p.Ala507= (c.1521C>T) is associated with neuropathy, hereditary sensory, type 1F (ClinVar).

How common is ATL3 p.Ala507= (c.1521C>T) in the general population?

ATL3 p.Ala507= (c.1521C>T) is rare (popmax 0.142%, nfe) (gnomAD).

ATL3 p.Ala507=

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.1521C>T · rs200026815 · VCV474836

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 6 submitters

gnomAD v4.1

Rare

rare (popmax 0.142%, nfe)

Conditions

neuropathy, hereditary sensory, type 1F

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 -2.8	GERP -4.3
Overall
CADD	8.099	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.142% European (non-Finnish) · 1,672/1,178,956 alleles

Filtering AF 0.136% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.134%

Overall 0.116% 1,875/1,612,034 alleles · rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.142%	705
Remaining individualsnot grpmax-eligible	0.122%	821
Middle Eastern	0.0839%	1,192
South Asian	0.0606%	1,651
East Asian	0.0423%	2,362
African / African-American	0.0387%	2,582
Admixed American	0.0284%	3,521
Finnishnot grpmax-eligible	0.00313%	31,962

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: ATL3
Protein: p.Ala507=
Coding: c.1521C>T
MANE Select: NM_015459
dbSNP: rs200026815
Type: single nucleotide variant
Location: chr11:63631058 (GRCh38)
Gene constraint: LOEUF 0.891 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 87.30 · 2 PDB

Full ATL3 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

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

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

Inheritance: Autosomal dominant
Onset: All ages

Similar variants

ATL3 c.1035+1G>A Uncertain significance ★★ same condition
ATL3 c.46+1G>A Uncertain significance ★★ same condition
ATL3 c.619-4A>G Uncertain significance ★★ same condition
ATL3 c.711+1G>T Uncertain significance ★★ same condition
ATL3 c.850+5G>A Uncertain significance ★★ same condition
ATL3 p.Ala457Val Uncertain significance ★★ ⚠ same condition
ATL3 p.Ala508Thr Uncertain significance ★★ ⚠ same condition
ATL3 p.Ala540Ser Uncertain significance ★★ ⚠ 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/atl3-p-ala507 (accessed [today's date]).

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