GAN p.Val438=
c.1314A>G · rs1267654719 · VCV3035684
Likely benign
No assertion criteria
Classification
Likely benign
ClinVar
Review
No assertion criteria ☆☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.00167%, amr)
Conditions
1
GAN-related disorder
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 0.29, phastCons 1 |
| Overall | ||
| CADD | 5.646 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00167%
Admixed American · 1/60,006 alleles
Overall
0.000124%
2/1,613,592 alleles · very rare
exomes 1/1,461,394 · genomes 1/152,198 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Admixed Americangrpmax | 0.00167% | 60,006 |
| African / African-American | 0.00133% | 74,912 |
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.Val438=
- Coding
- c.1314A>G
- MANE Select
- NM_022041
- dbSNP
- rs1267654719
- Type
- single nucleotide variant
- Location
- chr16:81365051 (GRCh38)
- Gene constraint
- LOEUF 0.842 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 89.93 · 2 PDB
- Residue 438
- a UniProt-annotated variant site (found in hereditary motor and sensory neuropathy; likely pathogenic)
Disease context
GAN-related disorder
Similar variants
- GAN p.Val438Ile Uncertain significance ⚠ same residue
- GAN c.1612+1G>C Likely pathogenic ★ same condition
- GAN p.Arg269Trp Conflicting classifications of pathogenicity ★ ⚠ same condition
- GAN c.1502+1G>T Pathogenic/Likely pathogenic ★★ same type
- GAN c.851+1G>A Pathogenic/Likely pathogenic ★★ same type
- GAN p.Arg545His Pathogenic/Likely pathogenic ★★ same type
- GAN p.Gln103Ter Pathogenic ★★ same type
- GAN p.Glu486Lys Pathogenic/Likely pathogenic ★★ ⚠ same type
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-val438 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown