Is GAN p.Ter598= (c.*1GGA[1]) pathogenic?

GAN p.Ter598= (c.1GGA[1]) is classified Likely benign in GAN (ClinVar, Single submitter, 1 submitter; last evaluated 2021-04-10). Ultra-rare (popmax 0.0911%, sas); Associated with giant axonal neuropathy 1.

What condition is associated with GAN p.Ter598= (c.*1GGA[1])?

GAN p.Ter598= (c.*1GGA[1]) is associated with giant axonal neuropathy 1 (ClinVar).

How common is GAN p.Ter598= (c.*1GGA[1]) in the general population?

GAN p.Ter598= (c.*1GGA[1]) is ultra-rare (popmax 0.0911%, sas) (gnomAD).

How is Giant axonal neuropathy inherited?

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

GAN p.Ter598=

c.*1GGA[1] · rs781299447 · VCV1573878

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

stop-loss

predicted LoF

gnomAD v4.1

Rare

ultra-rare (popmax 0.0911%, sas)

Conditions

giant axonal neuropathy 1

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	stop-loss	predicted loss-of-function
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 7.9	GERP 2.1, phastCons 1
Overall
CADD	10.27	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 0.0911% South Asian · 83/91,060 alleles

Filtering AF 0.0753% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0694%

Overall 0.00533% 86/1,613,786 alleles · ultra-rare exomes 82/1,461,564 · genomes 4/152,222 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0911%	1,097
Remaining individualsnot grpmax-eligible	0.0016%	62,498
European (non-Finnish)	0.00017%	589,887

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: GAN
Protein: p.Ter598=
Coding: c.*1GGA[1]
MANE Select: NM_022041
dbSNP: rs781299447
Type: Microsatellite
Location: chr16:81377595 (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.Ter598GluextTer? Uncertain significance ★★ same residue
GAN c.282+7_282+9del Benign/Likely benign ★★ same condition
GAN p.Lys45del Uncertain significance ★ same condition
GAN p.Val106del Conflicting classifications of pathogenicity ★ same condition
GAN c.1086+19_1086+22del Likely benign ★ same condition
GAN c.1086+25_1086+28del Benign ★ same condition
GAN c.1502+1G>T Pathogenic/Likely pathogenic ★★ same condition
GAN c.851+1G>A Pathogenic/Likely pathogenic ★★ 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-ter598 (accessed [today's date]).

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