FAT4 p.Pro4591=
c.13773C>T · rs369619007 · VCV2971673
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
very rare (popmax 0.000763%, nfe)
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 -0.98 | GERP -0.41, phastCons 0.002 |
| Overall | ||
| CADD | 3.404 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.000763%
European (non-Finnish) · 9/1,180,036 alleles
Filtering AF
0.000359%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00026%
Overall
0.000558%
9/1,614,020 alleles · very rare
exomes 8/1,461,886 · genomes 1/152,134 · joint denominator
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
- FAT4
- Protein
- p.Pro4591=
- Coding
- c.13773C>T
- MANE Select
- NM_001291303
- dbSNP
- rs369619007
- Type
- single nucleotide variant
- Location
- chr4:125490589 (GRCh38)
- Gene constraint
- LOEUF 0.317 · pLI 1.00 (gnomAD)
Similar variants
- FAT4 p.Pro4591Arg Uncertain significance ★ same residue
- FAT4 p.Arg1902Ter Pathogenic/Likely pathogenic ★★ same type
- FAT4 p.Arg2234Ter Pathogenic/Likely pathogenic ★★ same type
- FAT4 p.Gln4530Ter Pathogenic/Likely pathogenic ★★ same type
- FAT4 p.Glu2502Ter Pathogenic/Likely pathogenic ★★ same type
- FAT4 c.5307+6T>A Uncertain significance ★★ same type
- FAT4 c.6843+4A>G Uncertain significance ★★ same type
- FAT4 p.Ala1020Val 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/fat4-p-pro4591 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown