FAT4 p.Pro432=
c.1296T>C · rs372007282 · VCV390595
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 4 submitters
gnomAD v4.1
Rare
rare (popmax 0.132%, 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 -3.9 | GERP -4.8 |
| Overall | ||
| CADD | 7.361 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.132%
Middle Eastern · 8/6,062 alleles
Filtering AF
0.0656%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0478%
Overall
0.0167%
269/1,614,086 alleles · rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Middle Easterngrpmax | 0.132% | 758 |
| Admixed American | 0.0483% | 2,070 |
| Remaining individualsnot grpmax-eligible | 0.0336% | 2,977 |
| South Asian | 0.0209% | 4,794 |
| European (non-Finnish) | 0.0158% | 6,344 |
| African / African-American | 0.00533% | 18,765 |
| Finnishnot grpmax-eligible | 0.00313% | 31,972 |
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.Pro432=
- Coding
- c.1296T>C
- MANE Select
- NM_001291303
- dbSNP
- rs372007282
- Type
- single nucleotide variant
- Location
- chr4:125317707 (GRCh38)
- Gene constraint
- LOEUF 0.317 · pLI 1.00 (gnomAD)
- Residue 432
- a β-strand; the cadherin 4 domain
Similar variants
- 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
- FAT4 p.Ala1032Val 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-pro432 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown