FIG4 p.Asp452=
c.1356T>C · rs1777130180 · VCV916996
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
very rare (popmax 0.000509%, nfe)
Conditions
1
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 1.2 | GERP 0.85, phastCons 1 |
| Overall | ||
| CADD | 9.295 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.000509%
European (non-Finnish) · 6/1,178,048 alleles
Filtering AF
0.000183%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00012%
Overall
0.000372%
6/1,611,982 alleles · very rare
exomes 6/1,459,646 · genomes 0/152,336 · joint denominator
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.Asp452=
- Coding
- c.1356T>C
- MANE Select
- NM_014845
- dbSNP
- rs1777130180
- Type
- single nucleotide variant
- Location
- chr6:109762175 (GRCh38)
- Gene constraint
- LOEUF 0.966 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 80.65 · 1 PDB
- Residue 452
- the sac domain
Similar variants
- FIG4 p.Asp452Gly Uncertain significance ★ ⚠ same residue
- FIG4 c.1949-10T>G Pathogenic/Likely pathogenic ★★ same condition
- FIG4 c.877-2A>C Pathogenic/Likely pathogenic ★★ same condition
- FIG4 p.Gln823Ter Pathogenic/Likely pathogenic ★★ same condition
- FIG4 c.2096+3A>G Uncertain significance ★★ same condition
- FIG4 c.2460-8A>G Uncertain significance ★★ same condition
- FIG4 p.Arg899Ter Uncertain significance ★★ same condition
- FIG4 p.Gly445Asp Uncertain significance ★★ ⚠ 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-asp452 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown