FECH p.Lys106=
c.318G>A · VCV3635003
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.078%, eas)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation/SpliceAI carries the signal. | ||
| Splicing | ||
| SpliceAI | Δ0.42 | acceptor loss · deltas |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP 0.79 | GERP -1.1, phastCons 1 |
| Overall | ||
| CADD | 9.52 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.078%
East Asian · 35/44,874 alleles
Filtering AF
0.0576%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0506%
Overall
0.0026%
42/1,613,984 alleles · ultra-rare
exomes 41/1,461,886 · genomes 1/152,098 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| East Asiangrpmax | 0.078% | 1,282 |
| South Asian | 0.00769% | 13,009 |
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.Lys106=
- Coding
- c.318G>A
- MANE Select
- NM_000140
- Type
- single nucleotide variant
- Location
- chr18:57571537 (GRCh38)
- Gene constraint
- LOEUF 0.859 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 87.37 · 25 PDB
- Residue 106
- 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-lys106 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown