Is GAN p.Ser52Arg (c.156C>A) pathogenic?

GAN p.Ser52Arg (c.156C>A) is classified Uncertain significance in GAN (ClinVar, Single submitter, 1 submitter; last evaluated 2023-05-20). AlphaMissense: likely pathogenic (0.9998); No allele count reported in gnomAD v4.1 (AN 1,564,268); Associated with giant axonal neuropathy 1.

What condition is associated with GAN p.Ser52Arg (c.156C>A)?

GAN p.Ser52Arg (c.156C>A) is associated with giant axonal neuropathy 1 (ClinVar).

How common is GAN p.Ser52Arg (c.156C>A) in the general population?

GAN p.Ser52Arg (c.156C>A) is no allele count reported in gnomAD v4.1 (AN 1,564,268) (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.Ser52Arg (c.156C>A)?

AlphaMissense predicts likely pathogenic (score 0.9998) — an in-silico prediction, not a clinical call.

GAN p.Ser52Arg

c.156C>A · VCV3367053

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9998 · ACMG-weighted

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 1,564,268)

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

giant axonal neuropathy 1

Computational evidence

Protein change
AlphaMissense	0.9998	likely pathogenic · top 1% in GAN
REVEL	0.781	moderately pathogenic-leaning
SaProt	LLR -17.76	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 0.47	GERP -2, phastCons 1
Regional constraint	o/e 1.21	unconstrained · MANE · 62 kb · p 1.3e-08 · regional, not allelic
Overall
CADD	25.4	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — a triage signal, not a reclassification

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

Population frequency

gnomAD v4.1 · exomes + genomes

No allele count reported in gnomAD v4.1 (AN 1,564,268). This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: GAN
Protein: p.Ser52Arg
Coding: c.156C>A
MANE Select: NM_022041
Type: single nucleotide variant
Location: chr16:81315269 (GRCh38)
Gene constraint: LOEUF 0.842 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 89.93 · 2 PDB
Residue 52: 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.Ser52= Likely benign ★★ same residue
GAN p.Ser52Gly 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

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-ser52arg (accessed [today's date]).

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