FERMT1 p.Asp512=
c.1536T>C · VCV4769052
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.00133%, 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 2.3 | GERP -0.73, phastCons 1 |
| Overall | ||
| CADD | 6.862 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00133%
African / African-American · 1/74,922 alleles
Filtering AF
6.8e-05%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 1.9e-05%
Overall
0.000248%
4/1,614,068 alleles · very rare
exomes 3/1,461,892 · genomes 1/152,176 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 0.00133% | 74,922 |
| European (non-Finnish) | 0.000254% | 393,346 |
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.Asp512=
- Coding
- c.1536T>C
- MANE Select
- NM_017671
- Type
- single nucleotide variant
- Location
- chr20:6085123 (GRCh38)
- Gene constraint
- LOEUF 0.871 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 81.14
- Residue 512
- 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-asp512 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown