FER p.Leu547=
c.1641G>T · rs781568132 · VCV755254
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.0201%, afr)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP 1.2 | GERP 0.44, phastCons 1 |
| Overall | ||
| CADD | 6.079 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0201%
African / African-American · 15/74,722 alleles
Filtering AF
0.0123%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00991%
Overall
0.00124%
20/1,610,526 alleles · ultra-rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 0.0201% | 4,981 |
| Admixed American | 0.00502% | 19,911 |
| Remaining individualsnot grpmax-eligible | 0.00321% | 31,162 |
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
- FER
- Protein
- p.Leu547=
- Coding
- c.1641G>T
- MANE Select
- NM_005246
- dbSNP
- rs781568132
- Type
- single nucleotide variant
- Location
- chr5:108959332 (GRCh38)
- Gene constraint
- LOEUF 0.723 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 88.29 · 2 PDB
- Residue 547
- the sh2 domain
Similar variants
- FER p.Leu547Val Uncertain significance ★ ⚠ same residue
- FER p.Ala272Thr Uncertain significance ★ ⚠ same type
- FER p.Ala313Gly Uncertain significance ★ ⚠ same type
- FER p.Ala438Ser Uncertain significance ★ ⚠ same type
- FER p.Ala89Thr Uncertain significance ★ ⚠ same type
- FER p.Arg417Ser Uncertain significance ★ ⚠ same type
- FER p.Arg707His Uncertain significance ★ ⚠ same type
- FER p.Asn148Ile 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/fer-p-leu547 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown