FIG4 p.Glu609=
c.1827G>A · rs756085095 · VCV1604819
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
very rare (popmax 0.00678%, nfe)
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. | ||
| REVEL | 0.359 | indeterminate |
|---|---|---|
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
| Constraint at this position | ||
| Conservation | phyloP 0.35 | GERP 1.1, phastCons 0.49 |
| Overall | ||
| CADD | 4.86 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00678%
European (non-Finnish) · 80/1,179,412 alleles
Filtering AF
0.00555%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00514%
Overall
0.00561%
82/1,461,118 alleles · very rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| European (non-Finnish)grpmax | 0.00678% | 14,743 |
| Remaining individualsnot grpmax-eligible | 0.0032% | 31,231 |
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.Glu609=
- Coding
- c.1827G>A
- MANE Select
- NM_014845
- dbSNP
- rs756085095
- Type
- single nucleotide variant
- Location
- chr6:109776998 (GRCh38)
- Gene constraint
- LOEUF 0.966 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 80.65 · 1 PDB
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-glu609 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown