FAT4 p.Pro1844=
c.5532C>T · rs374897074 · VCV1622460
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
ultra-rare (popmax 0.0165%, 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 -7.1 | GERP -5 |
| Overall | ||
| CADD | 0.158 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0165%
Middle Eastern · 1/6,074 alleles
Filtering AF
0.00143%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.000891%
Overall
0.00167%
27/1,613,502 alleles · ultra-rare
exomes 21/1,461,436 · genomes 6/152,066 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Middle Easterngrpmax | 0.0165% | 6,074 |
| East Asian | 0.00446% | 22,426 |
| South Asian | 0.00439% | 22,769 |
| African / African-American | 0.00401% | 24,950 |
| Ashkenazi Jewishnot grpmax-eligible | 0.00338% | 29,586 |
| Remaining individualsnot grpmax-eligible | 0.0016% | 62,474 |
| Finnishnot grpmax-eligible | 0.00156% | 64,024 |
| European (non-Finnish) | 0.00119% | 84,264 |
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.Pro1844=
- Coding
- c.5532C>T
- MANE Select
- NM_001291303
- dbSNP
- rs374897074
- Type
- single nucleotide variant
- Location
- chr4:125407104 (GRCh38)
- Gene constraint
- LOEUF 0.317 · pLI 1.00 (gnomAD)
- Residue 1844
- the cadherin 18 domain
Similar variants
- FAT4 p.Pro1844Ser Conflicting classifications of pathogenicity ★ ⚠ 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-pro1844 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown