FIG4 p.Val435=
c.1305G>C · rs145227623 · VCV668151
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 5 submitters
gnomAD v4.1
Rare
ultra-rare (popmax 0.0156%, 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 4.5 | GERP 1.2, phastCons 1 |
| Overall | ||
| CADD | 10.93 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0156%
European (non-Finnish) · 184/1,179,314 alleles
Filtering AF
0.0138%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.013%
Overall
0.0122%
197/1,613,186 alleles · ultra-rare
exomes 181/1,461,010 · genomes 16/152,176 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| European (non-Finnish)grpmax | 0.0156% | 6,409 |
| Remaining individualsnot grpmax-eligible | 0.0128% | 7,806 |
| Admixed American | 0.005% | 19,999 |
| African / African-American | 0.00267% | 37,445 |
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.Val435=
- Coding
- c.1305G>C
- MANE Select
- NM_014845
- dbSNP
- rs145227623
- Type
- single nucleotide variant
- Location
- chr6:109762124 (GRCh38)
- Gene constraint
- LOEUF 0.966 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 80.65 · 1 PDB
- Residue 435
- 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-val435 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown