Is GAN p.Pro315Arg (c.944C>G) pathogenic?

GAN p.Pro315Arg (c.944C>G) is classified Uncertain significance in GAN (ClinVar, Single submitter, 1 submitter; last evaluated 2021-12-30). AlphaMissense: likely benign (0.2065); Very rare (popmax 0.00329%, sas); Associated with giant axonal neuropathy 1.

What condition is associated with GAN p.Pro315Arg (c.944C>G)?

GAN p.Pro315Arg (c.944C>G) is associated with giant axonal neuropathy 1 (ClinVar).

How common is GAN p.Pro315Arg (c.944C>G) in the general population?

GAN p.Pro315Arg (c.944C>G) is very rare (popmax 0.00329%, sas) (gnomAD).

How is Giant axonal neuropathy inherited?

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

What do computational predictors say about GAN p.Pro315Arg (c.944C>G)?

AlphaMissense predicts likely benign (score 0.2065) — an in-silico prediction, not a clinical call.

GAN p.Pro315Arg

c.944C>G · rs144486241 · VCV2140585

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2065 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00329%, sas)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Conditions

giant axonal neuropathy 1

Computational evidence

Protein change
AlphaMissense	0.2065	likely benign
REVEL	0.361	indeterminate
SaProt	LLR -10.20	damaging
⇒ SaProt calls this damaging; AlphaMissense does not; REVEL is indeterminate.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.6	GERP 2.4, phastCons 1
Regional constraint	o/e 1.21	unconstrained · MANE · 62 kb · p 1.3e-08 · regional, not allelic
Overall
CADD	23.0	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00329% South Asian · 3/91,074 alleles

Filtering AF 0.000875% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000443%

Overall 0.000558% 9/1,613,750 alleles · very rare exomes 8/1,461,516 · genomes 1/152,234 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.00329%	30,358
Admixed American	0.00167%	60,008
European (non-Finnish)	0.000424%	235,953

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.Pro315Arg
Coding: c.944C>G
MANE Select: NM_022041
dbSNP: rs144486241
Type: single nucleotide variant
Location: chr16:81357902 (GRCh38)
Gene constraint: LOEUF 0.842 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 89.93 · 2 PDB
Residue 315: 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.Pro315= Likely benign ★★ same residue
GAN p.Pro315Leu Conflicting classifications of pathogenicity ★ ⚠ 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

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-pro315arg (accessed [today's date]).

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