Is GAN p.Val164Ile (c.490G>A) pathogenic?

GAN p.Val164Ile (c.490G>A) is classified Uncertain significance in GAN (ClinVar, Multiple submitters, 4 submitters; last evaluated 2025-06-24). AlphaMissense: likely benign (0.1388); Very rare (popmax 0.00432%, nfe); Associated with Inborn genetic diseases.

What condition is associated with GAN p.Val164Ile (c.490G>A)?

GAN p.Val164Ile (c.490G>A) is associated with Inborn genetic diseases, giant axonal neuropathy 1 (ClinVar).

How common is GAN p.Val164Ile (c.490G>A) in the general population?

GAN p.Val164Ile (c.490G>A) is very rare (popmax 0.00432%, nfe) (gnomAD).

What do computational predictors say about GAN p.Val164Ile (c.490G>A)?

AlphaMissense predicts likely benign (score 0.1388) — an in-silico prediction, not a clinical call.

GAN p.Val164Ile

c.490G>A · rs778744880 · VCV1403425

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

AlphaMissense

likely benign

0.1388 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00432%, nfe)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.1388	likely benign
REVEL	0.44	indeterminate
SaProt	LLR -10.25	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 12	GERP 2.7, phastCons 1
Regional constraint	o/e 1.21	unconstrained · MANE · 62 kb · p 1.3e-08 · regional, not allelic
Overall
CADD	26.6	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 0.00432% European (non-Finnish) · 51/1,179,868 alleles

Filtering AF 0.00334% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00302%

Overall 0.00341% 55/1,613,874 alleles · very rare exomes 51/1,461,716 · genomes 4/152,158 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00432%	23,135
Remaining individualsnot grpmax-eligible	0.0032%	31,240
Finnishnot grpmax-eligible	0.00156%	64,018
African / African-American	0.00133%	74,922

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.Val164Ile
Coding: c.490G>A
MANE Select: NM_022041
dbSNP: rs778744880
Type: single nucleotide variant
Location: chr16:81354612 (GRCh38)
Gene constraint: LOEUF 0.842 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 89.93 · 2 PDB
Residue 164: the back domain; an α-helix

Full GAN gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: giant axonal neuropathy 1

Similar variants

GAN p.Val164= Likely benign ★★ 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-val164ile (accessed [today's date]).

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