Is GAN p.Pro513= (c.1539C>T) pathogenic?

GAN p.Pro513= (c.1539C>T) is classified Likely benign in GAN (ClinVar, Multiple submitters, 2 submitters; last evaluated 2024-11-21). Ultra-rare (popmax 0.0245%, eas); Associated with giant axonal neuropathy 1.

What condition is associated with GAN p.Pro513= (c.1539C>T)?

GAN p.Pro513= (c.1539C>T) is associated with giant axonal neuropathy 1 (ClinVar).

How common is GAN p.Pro513= (c.1539C>T) in the general population?

GAN p.Pro513= (c.1539C>T) is ultra-rare (popmax 0.0245%, eas) (gnomAD).

How is Giant axonal neuropathy inherited?

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

GAN p.Pro513=

c.1539C>T · rs774396975 · VCV1138992

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0245%, eas)

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 -13	GERP -4.4
Overall
CADD	0.444	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0245% East Asian · 11/44,866 alleles

Filtering AF 0.0137% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0106%

Overall 0.00186% 30/1,611,622 alleles · ultra-rare exomes 21/1,459,396 · genomes 9/152,226 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.0245%	4,079
Remaining individualsnot grpmax-eligible	0.0016%	62,420
European (non-Finnish)	0.00144%	69,279
African / African-American	0.00133%	74,976

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.Pro513=
Coding: c.1539C>T
MANE Select: NM_022041
dbSNP: rs774396975
Type: single nucleotide variant
Location: chr16:81377255 (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.Pro513Ala 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-pro513 (accessed [today's date]).

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