Is GAN p.Ala2= (c.6T>G) pathogenic?

GAN p.Ala2= (c.6T>G) is classified Likely benign in GAN (ClinVar, Single submitter, 1 submitter; last evaluated 2025-04-21). Very rare (popmax 8.89e-05%, nfe); Associated with giant axonal neuropathy 1.

What condition is associated with GAN p.Ala2= (c.6T>G)?

GAN p.Ala2= (c.6T>G) is associated with giant axonal neuropathy 1 (ClinVar).

How common is GAN p.Ala2= (c.6T>G) in the general population?

GAN p.Ala2= (c.6T>G) is very rare (popmax 8.89e-05%, nfe) (gnomAD).

How is Giant axonal neuropathy inherited?

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

GAN p.Ala2=

c.6T>G · rs980975991 · VCV1989090

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 8.89e-05%, nfe)

Conditions

giant axonal neuropathy 1

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -0.86	GERP -1.7, phastCons 0.006
Overall
CADD	12.98	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 8.89e-05% European (non-Finnish) · 1/1,124,508 alleles

Overall 0.000133% 2/1,502,812 alleles · very rare exomes 2/1,350,994 · genomes 0/151,818 · joint denominator

Ancestry group	Frequency	1 in
Remaining individualsnot grpmax-eligible	0.00173%	57,650
European (non-Finnish)grpmax	8.89e-05%	1,124,508

Remaining individuals shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Ala2=
Coding: c.6T>G
MANE Select: NM_022041
dbSNP: rs980975991
Type: single nucleotide variant
Location: chr16:81315119 (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.Ala2Thr Uncertain significance ★ ⚠ same residue
GAN c.1502+1G>T Pathogenic/Likely pathogenic ★★ same condition
GAN c.851+1G>A Pathogenic/Likely pathogenic ★★ same condition
GAN p.Arg545His Pathogenic/Likely pathogenic ★★ same condition
GAN p.Gln103Ter Pathogenic ★★ same condition
GAN p.Glu486Lys Pathogenic/Likely pathogenic ★★ ⚠ same condition
GAN c.1373+4C>T Uncertain significance ★★ same condition
GAN c.1612+4A>G 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/gan-p-ala2 (accessed [today's date]).

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