FECH p.Ala382=
c.1146C>T · rs146918011 · VCV1561579
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
rare (popmax 0.135%, afr)
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 -6.2 | GERP -3.8 |
| Overall | ||
| CADD | 1.114 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.135%
African / African-American · 101/75,034 alleles
Filtering AF
0.113%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.105%
Overall
0.0103%
167/1,613,750 alleles · rare
exomes 89/1,461,456 · genomes 78/152,294 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 0.135% | 743 |
| Remaining individualsnot grpmax-eligible | 0.0304% | 3,288 |
| Admixed American | 0.0117% | 8,575 |
| Finnishnot grpmax-eligible | 0.00469% | 21,327 |
| South Asian | 0.00439% | 22,762 |
| European (non-Finnish) | 0.0028% | 35,758 |
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.Ala382=
- Coding
- c.1146C>T
- MANE Select
- NM_000140
- dbSNP
- rs146918011
- Type
- single nucleotide variant
- Location
- chr18:57550838 (GRCh38)
- Gene constraint
- LOEUF 0.859 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 87.37 · 25 PDB
- Residue 382
- an α-helix
Similar variants
- FECH c.1137+3A>G Pathogenic/Likely pathogenic ★★ same type
- FECH c.314+2T>G Pathogenic/Likely pathogenic ★★ same type
- FECH c.463+1G>C Pathogenic ★★ same type
- FECH c.598+1G>T Pathogenic ★★ same type
- FECH c.599-2A>G Pathogenic ★★ same type
- FECH c.913-2A>G Likely pathogenic ★★ same type
- FECH p.Arg115Ter Pathogenic/Likely pathogenic ★★ same type
- FECH p.Arg298Ter Pathogenic/Likely pathogenic ★★ same type
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-ala382 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown