FERMT1 p.Ala359=
c.1077G>A · rs34569233 · VCV1566768
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 3 submitters
gnomAD v4.1
Rare
ultra-rare (popmax 0.0454%, afr)
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 -7.7 | GERP -4.4 |
| Overall | ||
| CADD | 1.32 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0454%
African / African-American · 34/74,882 alleles
Filtering AF
0.0334%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0292%
Overall
0.00682%
110/1,613,156 alleles · ultra-rare
exomes 77/1,461,276 · genomes 33/151,880 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 0.0454% | 2,202 |
| Admixed American | 0.035% | 2,854 |
| Middle Eastern | 0.0165% | 6,056 |
| South Asian | 0.0132% | 7,589 |
| Remaining individualsnot grpmax-eligible | 0.0048% | 20,823 |
| European (non-Finnish) | 0.00331% | 30,247 |
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.Ala359=
- Coding
- c.1077G>A
- MANE Select
- NM_017671
- dbSNP
- rs34569233
- Type
- single nucleotide variant
- Location
- chr20:6096914 (GRCh38)
- Gene constraint
- LOEUF 0.871 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 81.14
- Residue 359
- the ferm domain
Similar variants
- FERMT1 p.Ala359Val 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-ala359 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown