FAT4 p.Pro4545=
c.13635G>A · rs757657669 · VCV1644110
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
ultra-rare (popmax 0.0493%, mid)
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 -8 | GERP -3.1 |
| Overall | ||
| CADD | 0.366 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0493%
Middle Eastern · 3/6,084 alleles
Filtering AF
0.0134%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00715%
Overall
0.00186%
30/1,614,016 alleles · ultra-rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Middle Easterngrpmax | 0.0493% | 2,028 |
| Admixed American | 0.00667% | 15,002 |
| South Asian | 0.00659% | 15,181 |
| Remaining individualsnot grpmax-eligible | 0.0064% | 15,620 |
| East Asian | 0.00223% | 44,866 |
| African / African-American | 0.00134% | 74,894 |
| European (non-Finnish) | 0.000932% | 107,277 |
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.Pro4545=
- Coding
- c.13635G>A
- MANE Select
- NM_001291303
- dbSNP
- rs757657669
- Type
- single nucleotide variant
- Location
- chr4:125490451 (GRCh38)
- Gene constraint
- LOEUF 0.317 · pLI 1.00 (gnomAD)
- Residue 4545
- the 'disordered' region
Similar variants
- FAT4 p.Pro4545Gln Uncertain significance ★ ⚠ same residue
- FAT4 p.Pro4545Leu Conflicting classifications of pathogenicity ★ ⚠ same residue
- FAT4 p.Pro4545Ser 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
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-pro4545 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown