FECH p.Arg367Ter
c.1099A>T · VCV3346176
Pathogenic
No assertion criteria
Classification
Pathogenic
ClinVar
Review
No assertion criteria ☆☆☆☆
ClinVar · 1 submitter
Consequence
nonsense (stop-gain)
predicted LoF
gnomAD v4.1
Absent
absent from gnomAD v4.1
Conditions
1
FECH-related disorder
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Consequence | nonsense (stop-gain) | predicted loss-of-function |
|---|---|---|
| NMD | escapes | premature termination codon within the last 50 nt of the penultimate exon (10 of 11, 38 nt from its 3' end) — the truncated protein is likely expressed. PVS1 input, not an applied code |
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
| Pangolin | Δ0.42 | loss · gain 0.00 · not in the SpliceAI release · independent |
| Constraint at this position | ||
| Conservation | phyloP 6.2 | GERP 0.73, phastCons 1 |
| Overall | ||
| CADD | 38.0 | PHRED · no single calibrated threshold — expert panels disagree |
Predicted loss-of-function is descriptive, not an applied PVS1 code.
Population frequency
gnomAD v4.1 · exomes + genomes
Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.
Variant & gene context
- Gene
- FECH
- Protein
- p.Arg367Ter
- Coding
- c.1099A>T
- MANE Select
- NM_000140
- Type
- single nucleotide variant
- Location
- chr18:57551353 (GRCh38)
- Gene constraint
- LOEUF 0.859 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 87.37 · 25 PDB
- Residue 367
- a β-strand
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-arg367ter (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown