FERMT1 p.Pro141=
c.423G>A · rs41308076 · VCV1625146
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
ultra-rare (popmax 0.0353%, 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 2.3 | GERP -1.7, phastCons 1 |
| Overall | ||
| CADD | 13.38 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0353%
Middle Eastern · 2/5,672 alleles
Filtering AF
0.0087%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00691%
Overall
0.00394%
63/1,598,468 alleles · ultra-rare
exomes 60/1,446,294 · genomes 3/152,174 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Middle Easterngrpmax | 0.0353% | 2,836 |
| South Asian | 0.0147% | 6,787 |
| Remaining individualsnot grpmax-eligible | 0.0129% | 7,734 |
| East Asian | 0.00671% | 14,913 |
| African / African-American | 0.00538% | 18,604 |
| Finnishnot grpmax-eligible | 0.00318% | 31,457 |
| European (non-Finnish) | 0.00265% | 37,792 |
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.Pro141=
- Coding
- c.423G>A
- MANE Select
- NM_017671
- dbSNP
- rs41308076
- Type
- single nucleotide variant
- Location
- chr20:6112586 (GRCh38)
- Gene constraint
- LOEUF 0.871 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 81.14
- Residue 141
- the ferm domain
Similar variants
- FERMT1 p.Pro141Leu Uncertain significance ★★ ⚠ same residue
- 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
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-pro141 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown