FERMT1 p.Ala286=
c.858T>C · VCV4694452
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.0379%, eas)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Splicing | ||
| SpliceAI | <0.2 | no splice effect predicted · four deltas, not one · how we know |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP -0.064 | GERP -2, phastCons 0.005 |
| Overall | ||
| CADD | 9.357 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0379%
East Asian · 17/44,838 alleles
Filtering AF
0.0241%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0198%
Overall
0.00112%
18/1,611,550 alleles · ultra-rare
exomes 15/1,459,286 · genomes 3/152,264 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| East Asiangrpmax | 0.0379% | 2,638 |
| Admixed American | 0.00167% | 60,002 |
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
- FERMT1
- Protein
- p.Ala286=
- Coding
- c.858T>C
- MANE Select
- NM_017671
- Type
- single nucleotide variant
- Location
- chr20:6097623 (GRCh38)
- Gene constraint
- LOEUF 0.871 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 81.14
- Residue 286
- the ferm domain
Similar variants
- FERMT1 c.1371+4A>G Pathogenic ★★ same type
- FERMT1 c.532+1G>A Likely pathogenic ★★ same type
- FERMT1 p.Arg110Ter Pathogenic ★★ same type
- FERMT1 p.Arg271Ter Pathogenic ★★ same type
- FERMT1 p.Arg288Ter Pathogenic ★★ same type
- FERMT1 p.Glu304Ter Pathogenic ★★ same type
- FERMT1 p.Trp298Ter Pathogenic ★★ same type
- FERMT1 c.*1004G>A Uncertain significance ★★ 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/fermt1-p-ala286 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown