Is GAN p.Arg84= (c.252A>G) pathogenic?

GAN p.Arg84= (c.252A>G) is classified Likely benign in GAN (ClinVar, Single submitter, 1 submitter; last evaluated 2023-05-15). Very rare (popmax 0.00136%, afr); Associated with giant axonal neuropathy 1.

What condition is associated with GAN p.Arg84= (c.252A>G)?

GAN p.Arg84= (c.252A>G) is associated with giant axonal neuropathy 1 (ClinVar).

How common is GAN p.Arg84= (c.252A>G) in the general population?

GAN p.Arg84= (c.252A>G) is very rare (popmax 0.00136%, afr) (gnomAD).

How is Giant axonal neuropathy inherited?

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

GAN p.Arg84=

c.252A>G · rs1435557918 · VCV2092904

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00136%, afr)

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 5.4	GERP 0.086, phastCons 1
Overall
CADD	11.54	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00136% African / African-American · 1/73,464 alleles

Overall 0.00013% 2/1,535,708 alleles · very rare exomes 2/1,383,402 · genomes 0/152,306 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00136%	73,464
South Asian	0.00112%	89,514

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.Arg84=
Coding: c.252A>G
MANE Select: NM_022041
dbSNP: rs1435557918
Type: single nucleotide variant
Location: chr16:81351667 (GRCh38)
Gene constraint: LOEUF 0.842 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 89.93 · 2 PDB
Residue 84: the btb domain; an α-helix

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 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
GAN c.283-3T>A 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-arg84 (accessed [today's date]).

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