Is GAN p.Pro288fs (c.861dup) pathogenic?

GAN p.Pro288fs (c.861dup) is classified Pathogenic in GAN (ClinVar, Single submitter, 1 submitter; last evaluated 2023-04-11). No gnomAD frequency available for this variant; Associated with giant axonal neuropathy 1.

What condition is associated with GAN p.Pro288fs (c.861dup)?

GAN p.Pro288fs (c.861dup) is associated with giant axonal neuropathy 1 (ClinVar).

How common is GAN p.Pro288fs (c.861dup) in the general population?

GAN p.Pro288fs (c.861dup) is no gnomAD frequency available for this variant (gnomAD).

How is Giant axonal neuropathy inherited?

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

GAN p.Pro288fs

c.861dup · rs2507735150 · VCV2498221

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Not reported

no gnomAD frequency available for this variant

Conditions

giant axonal neuropathy 1

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 5 of 11
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 7.5	GERP 1.6, 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: GAN
Protein: p.Pro288fs
Coding: c.861dup
MANE Select: NM_022041
dbSNP: rs2507735150
Type: Duplication
Location: chr16:81357816 (GRCh38)
Gene constraint: LOEUF 0.842 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 89.93 · 2 PDB

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

Disease context

giant axonal neuropathy 1 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Giant axonal neuropathy (Orphanet):

Inheritance: Autosomal recessive
Onset: Childhood, Infancy

Similar variants

GAN p.Pro288Ala Uncertain significance ★ ⚠ same residue
GAN p.Lys72fs Pathogenic ★ same condition
GAN p.Pro301_Asn302insTer Pathogenic ★ same condition
GAN p.Thr101fs Pathogenic ★ same condition
GAN p.Asp564fs Uncertain significance ★ same condition
GAN p.Pro288Arg Uncertain significance ★ ⚠ same residue
GAN p.Pro288Leu Uncertain significance ★ ⚠ same residue
GAN c.1502+11dup 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/gan-p-pro288fs (accessed [today's date]).

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