FECH p.Leu384=
c.1152G>A · rs147782079 · VCV3031362
Likely benign
No assertion criteria
Classification
Likely benign
ClinVar
Review
No assertion criteria ☆☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.0546%, afr)
Conditions
1
FECH-related disorder
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 2.7 | GERP 1.9, phastCons 1 |
| Overall | ||
| CADD | 10.26 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0546%
African / African-American · 41/75,036 alleles
Filtering AF
0.0413%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0367%
Overall
0.00316%
51/1,613,872 alleles · ultra-rare
exomes 22/1,461,568 · genomes 29/152,304 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 0.0546% | 1,830 |
| Admixed American | 0.00666% | 15,006 |
| Remaining individualsnot grpmax-eligible | 0.0016% | 62,482 |
| European (non-Finnish) | 0.000424% | 236,003 |
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
- FECH
- Protein
- p.Leu384=
- Coding
- c.1152G>A
- MANE Select
- NM_000140
- dbSNP
- rs147782079
- Type
- single nucleotide variant
- Location
- chr18:57550832 (GRCh38)
- Gene constraint
- LOEUF 0.859 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 87.37 · 25 PDB
- Residue 384
- an α-helix
Disease context
FECH-related disorder
Similar variants
- FECH c.314+2T>G Pathogenic/Likely pathogenic ★★ same condition
- FECH c.599-2A>G Pathogenic ★★ same condition
- FECH p.Arg298Ter Pathogenic/Likely pathogenic ★★ same condition
- FECH p.Arg96Ter Pathogenic/Likely pathogenic ★★ same condition
- FECH p.Glu359= Pathogenic/Likely pathogenic ★★ same condition
- FECH c.195-2A>T Pathogenic ★ same condition
- FECH c.706-3C>G Likely pathogenic ★ same condition
- FECH c.315-1G>C 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/fech-p-leu384 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown