FIG4 p.Asp294=
c.882T>C · rs776821372 · VCV737105
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.00334%, amr)
Conditions
1
Charcot-Marie-Tooth disease type 4
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Splicing | ||
| SpliceAI | <0.2 | all four deltas below 0.2 · T>G here scores Δ0.42 · evaluated, not missing |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP 0.45 | GERP -3.2, phastCons 1 |
| Overall | ||
| CADD | 6.986 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00334%
Admixed American · 2/59,920 alleles
Filtering AF
0.000554%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.000207%
Overall
0.000496%
8/1,612,186 alleles · very rare
exomes 8/1,459,892 · genomes 0/152,294 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Admixed Americangrpmax | 0.00334% | 29,960 |
| European (non-Finnish) | 0.000509% | 196,434 |
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
- FIG4
- Protein
- p.Asp294=
- Coding
- c.882T>C
- MANE Select
- NM_014845
- dbSNP
- rs776821372
- Type
- single nucleotide variant
- Location
- chr6:109743115 (GRCh38)
- Gene constraint
- LOEUF 0.966 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 80.65 · 1 PDB
- Residue 294
- the sac domain
Similar variants
- FIG4 c.1040-1G>A Likely pathogenic ★★ same condition
- FIG4 c.1584-1G>T Likely pathogenic ★★ same condition
- FIG4 c.1948+1G>A Likely pathogenic ★★ same condition
- FIG4 c.1949-10T>G Pathogenic/Likely pathogenic ★★ same condition
- FIG4 c.2459+1G>A Pathogenic ★★ same condition
- FIG4 c.877-2A>C Pathogenic/Likely pathogenic ★★ same condition
- FIG4 p.Arg152Ter Pathogenic/Likely pathogenic ★★ same condition
- FIG4 p.Arg183Ter 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/fig4-p-asp294 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown