FIG4 p.His386=
c.1158T>C · rs370557879 · VCV507749
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 3 submitters
gnomAD v4.1
Rare
ultra-rare (popmax 0.0121%, sas)
Conditions
2
Inborn genetic diseases
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 -5.3 | GERP -3.1 |
| Overall | ||
| CADD | 3.596 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0121%
South Asian · 11/91,078 alleles
Filtering AF
0.00676%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00522%
Overall
0.00508%
82/1,613,884 alleles · ultra-rare
exomes 82/1,461,570 · genomes 0/152,314 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| South Asiangrpmax | 0.0121% | 8,280 |
| Ashkenazi Jewishnot grpmax-eligible | 0.00676% | 14,800 |
| European (non-Finnish) | 0.00576% | 17,349 |
| Remaining individualsnot grpmax-eligible | 0.0016% | 62,498 |
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.His386=
- Coding
- c.1158T>C
- MANE Select
- NM_014845
- dbSNP
- rs370557879
- Type
- single nucleotide variant
- Location
- chr6:109760270 (GRCh38)
- Gene constraint
- LOEUF 0.966 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 80.65 · 1 PDB
- Residue 386
- 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-his386 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown