Is ATL3 p.Arg82Ter (c.244C>T) pathogenic?

ATL3 p.Arg82Ter (c.244C>T) is classified Uncertain significance in ATL3 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2024-02-04). Very rare (popmax 0.00223%, eas); Associated with neuropathy, hereditary sensory, type 1F.

What condition is associated with ATL3 p.Arg82Ter (c.244C>T)?

ATL3 p.Arg82Ter (c.244C>T) is associated with neuropathy, hereditary sensory, type 1F (ClinVar).

How common is ATL3 p.Arg82Ter (c.244C>T) in the general population?

ATL3 p.Arg82Ter (c.244C>T) is very rare (popmax 0.00223%, eas) (gnomAD).

ATL3 p.Arg82Ter

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.244C>T · rs772705343 · VCV1791459

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

Consequence

nonsense (stop-gain)

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.00223%, eas)

Conditions

neuropathy, hereditary sensory, type 1F

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	nonsense (stop-gain)	predicted loss-of-function
NMD	predicted	premature termination codon in exon 2 of 13
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 6.4	GERP 2.2, phastCons 1
Overall
CADD	39.0	PHRED · no single calibrated threshold — expert panels disagree

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00223% East Asian · 1/44,892 alleles

Filtering AF 0.000763% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000605%

Overall 0.00112% 18/1,613,680 alleles · very rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00223%	44,892
Remaining individualsnot grpmax-eligible	0.0016%	62,478
African / African-American	0.00134%	74,822
European (non-Finnish)	0.00127%	78,662

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.Arg82Ter
Coding: c.244C>T
MANE Select: NM_015459
dbSNP: rs772705343
Type: single nucleotide variant
Location: chr11:63659055 (GRCh38)
Gene constraint: LOEUF 0.891 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 87.30 · 2 PDB
Residue 82: an α-helix; 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.Arg82= Likely benign ★ same residue
ATL3 p.Arg82Gln Uncertain significance ★ same residue
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

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-arg82ter (accessed [today's date]).

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