FERMT1 p.Ala445=
c.1335C>T · rs751428620 · VCV1540325
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.0494%, mid)
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 0.046 | GERP -1.6, phastCons 0.054 |
| Overall | ||
| CADD | 14.33 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0494%
Middle Eastern · 3/6,078 alleles
Filtering AF
0.0134%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00716%
Overall
0.00224%
36/1,609,190 alleles · ultra-rare
exomes 33/1,457,082 · genomes 3/152,108 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Middle Easterngrpmax | 0.0494% | 2,026 |
| Admixed American | 0.015% | 6,666 |
| Remaining individualsnot grpmax-eligible | 0.00963% | 10,389 |
| South Asian | 0.00659% | 15,165 |
| African / African-American | 0.00401% | 24,923 |
| European (non-Finnish) | 0.000765% | 130,637 |
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.Ala445=
- Coding
- c.1335C>T
- MANE Select
- NM_017671
- dbSNP
- rs751428620
- Type
- single nucleotide variant
- Location
- chr20:6087813 (GRCh38)
- Gene constraint
- LOEUF 0.871 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 81.14
- Residue 445
- the ferm domain; the ph 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-ala445 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown