Is ATL3 p.Phe217fs (c.650del) pathogenic?

ATL3 p.Phe217fs (c.650del) is classified Uncertain significance in ATL3 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-07-19). Absent from gnomAD; Associated with neuropathy, hereditary sensory, type 1F.

What condition is associated with ATL3 p.Phe217fs (c.650del)?

ATL3 p.Phe217fs (c.650del) is associated with neuropathy, hereditary sensory, type 1F (ClinVar).

How common is ATL3 p.Phe217fs (c.650del) in the general population?

ATL3 p.Phe217fs (c.650del) is absent from gnomAD (gnomAD).

ATL3 p.Phe217fs

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.650del · rs1939792135 · VCV939592

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Not reported

no gnomAD frequency available for this variant

Conditions

neuropathy, hereditary sensory, type 1F

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function
NMD	predicted	premature termination codon in exon 7 of 13
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 1.5	GERP 0.47, phastCons 1

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

dbSNP / gnomAD

No gnomAD frequency available for this variant. This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: ATL3
Protein: p.Phe217fs
Coding: c.650del
MANE Select: NM_015459
dbSNP: rs1939792135
Type: Deletion
Location: chr11:63644230 (GRCh38)
Gene constraint: LOEUF 0.891 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 87.30 · 2 PDB
Residue 217: the gb1/rhd3-type g domain

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 p.Glu129del Uncertain significance ★★ same condition
ATL3 c.405+4del Uncertain significance ★ same condition
ATL3 c.850+3del Uncertain significance ★ same condition
ATL3 p.Gly334del Uncertain significance ★ same condition
ATL3 p.Gly488fs Uncertain significance ★ same condition
ATL3 p.Gly501del Uncertain significance ★ same condition
ATL3 p.Pro380fs Uncertain significance ★ same condition
ATL3 c.1108-8_1108-4del Likely benign ★ 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-phe217fs (accessed [today's date]).

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