FECH c.67+12T>C
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.00399%, amr)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Splicing | ||
| Splice region | donor +12 | near-intronic (+12 nt from the splice site) |
|---|---|---|
| SpliceAI | <0.2 | all four deltas below 0.2 · A>T here scores Δ0.41 · evaluated, not missing |
| Constraint at this position | ||
| Conservation | phyloP 0.012 | GERP -1.6 |
| Non-coding constraint | Z 3.39 | 1 kb window · o/e 0.74 · regional · uncalibrated |
| Overall | ||
| CADD | 14.2 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00399%
Admixed American · 2/50,158 alleles
Filtering AF
0.000661%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.000247%
Overall
0.000131%
2/1,520,982 alleles · very rare
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
- Coding
- c.67+12T>C
- MANE Select
- NM_000140
- Type
- single nucleotide variant
- Location
- chr18:57586542 (GRCh38)
- Gene constraint
- LOEUF 0.859 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 87.37 · 25 PDB
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-c-67-plus-12t-c (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown