GDAP1 p.Lys25=
c.75G>A · rs761730309 · VCV917089
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 3 submitters
gnomAD v4.1
Rare
very rare (popmax 0.00322%, nfe)
Conditions
2
Charcot-Marie-Tooth disease
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 3.7 | GERP -1.8, phastCons 1 |
| Overall | ||
| CADD | 13.1 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00322%
European (non-Finnish) · 38/1,178,988 alleles
Filtering AF
0.0024%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0021%
Overall
0.00242%
39/1,613,034 alleles · very rare
exomes 39/1,460,660 · genomes 0/152,374 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| European (non-Finnish)grpmax | 0.00322% | 31,026 |
| African / African-American | 0.00133% | 75,056 |
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
- GDAP1
- Protein
- p.Lys25=
- Coding
- c.75G>A
- MANE Select
- NM_018972
- dbSNP
- rs761730309
- Type
- single nucleotide variant
- Location
- chr8:74350536 (GRCh38)
- Gene constraint
- LOEUF 0.963 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 87.68 · 8 PDB
- Residue 25
- the gst n-terminal domain
Similar variants
- GDAP1 p.Lys25Glu Uncertain significance ★ ⚠ same residue
- GDAP1 c.311-1G>A Pathogenic/Likely pathogenic ★★ same condition
- GDAP1 c.579+1G>A Pathogenic ★★ same condition
- GDAP1 c.694+1G>A Pathogenic/Likely pathogenic ★★ same condition
- GDAP1 p.Arg120Trp Pathogenic ★★ ⚠ same condition
- GDAP1 p.Arg125Ter Pathogenic ★★ same condition
- GDAP1 p.Arg161His Pathogenic/Likely pathogenic ★★ ⚠ same condition
- GDAP1 p.Arg191Ter Pathogenic/Likely pathogenic ★★ 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/gdap1-p-lys25 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown