Is GAN p.Ser79= (c.237G>A) pathogenic?

GAN p.Ser79= (c.237G>A) is classified Likely benign in GAN (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-11-01). Ultra-rare (popmax 0.0623%, afr); Associated with giant axonal neuropathy 1.

What condition is associated with GAN p.Ser79= (c.237G>A)?

GAN p.Ser79= (c.237G>A) is associated with giant axonal neuropathy 1 (ClinVar).

How common is GAN p.Ser79= (c.237G>A) in the general population?

GAN p.Ser79= (c.237G>A) is ultra-rare (popmax 0.0623%, afr) (gnomAD).

How is Giant axonal neuropathy inherited?

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

GAN p.Ser79=

c.237G>A · rs144007114 · VCV513198

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0623%, 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 4.4	GERP 2.5, phastCons 1
Overall
CADD	14.42	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0623% African / African-American · 46/73,876 alleles

Filtering AF 0.048% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0429%

Overall 0.00352% 55/1,562,896 alleles · ultra-rare exomes 23/1,410,800 · genomes 32/152,096 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0623%	1,606
East Asian	0.00672%	14,877
Finnishnot grpmax-eligible	0.00313%	31,993
Admixed American	0.00167%	59,932
European (non-Finnish)	0.000265%	377,810

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.Ser79=
Coding: c.237G>A
MANE Select: NM_022041
dbSNP: rs144007114
Type: single nucleotide variant
Location: chr16:81351652 (GRCh38)
Gene constraint: LOEUF 0.842 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 89.93 · 2 PDB
Residue 79: the btb domain; a UniProt-annotated variant site (in gan1)

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.Ser79Leu 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-ser79 (accessed [today's date]).

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