FECH p.Glu359=
c.1077G>A · rs1223818578 · VCV2736733
Pathogenic/Likely pathogenic
Multiple submitters
Classification
Pathogenic/Likely pathogenic
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 3 submitters
gnomAD v4.1
Rare
very rare (popmax 0.00136%, nfe)
Conditions
1
FECH-related disorders
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation/SpliceAI carries the signal. | ||
| Splicing | ||
| SpliceAI | Δ0.80 | donor loss · deltas |
|---|---|---|
| Pangolin | Δ0.67 | loss · gain 0.04 · agrees with SpliceAI · independent |
| Constraint at this position | ||
| Conservation | phyloP 7.7 | GERP 1.9, phastCons 1 |
| Overall | ||
| CADD | 21.6 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00136%
European (non-Finnish) · 16/1,180,024 alleles
Filtering AF
0.000803%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00065%
Overall
0.00105%
17/1,614,066 alleles · very rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| European (non-Finnish)grpmax | 0.00136% | 73,752 |
| African / African-American | 0.00133% | 74,932 |
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.Glu359=
- Coding
- c.1077G>A
- MANE Select
- NM_000140
- dbSNP
- rs1223818578
- Type
- single nucleotide variant
- Location
- chr18:57554260 (GRCh38)
- Gene constraint
- LOEUF 0.859 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 87.37 · 25 PDB
- Residue 359
- an α-helix
Disease context
FECH-related disorders
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 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
- FECH p.Arg367Ter 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-glu359 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown