Is ATL3 p.Ser93Ter (c.278C>G) pathogenic?

ATL3 p.Ser93Ter (c.278C>G) is classified Uncertain significance in ATL3 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2024-07-24). Absent from gnomAD v4.1; Associated with neuropathy, hereditary sensory, type 1F.

What condition is associated with ATL3 p.Ser93Ter (c.278C>G)?

ATL3 p.Ser93Ter (c.278C>G) is associated with neuropathy, hereditary sensory, type 1F (ClinVar).

How common is ATL3 p.Ser93Ter (c.278C>G) in the general population?

ATL3 p.Ser93Ter (c.278C>G) is absent from gnomAD v4.1 (gnomAD).

ATL3 p.Ser93Ter

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.278C>G · VCV3600960

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

Consequence

nonsense (stop-gain)

predicted LoF

gnomAD v4.1

Absent

absent from gnomAD v4.1

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-escape possible for C-terminal truncations
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP 4.3	GERP 1.3, phastCons 1
Overall
CADD	37.0	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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: ATL3
Protein: p.Ser93Ter
Coding: c.278C>G
Type: single nucleotide variant
Location: chr11:63658888 (GRCh38)

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

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-ser93ter (accessed [today's date]).

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