FAT4 p.Ala653=
c.1959C>T · rs191491571 · VCV515429
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 3 submitters
gnomAD v4.1
Rare
ultra-rare (popmax 0.0573%, 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 -0.74 | GERP -3.5, phastCons 0.01 |
| Overall | ||
| CADD | 7.05 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0573%
African / African-American · 43/75,038 alleles
Filtering AF
0.0436%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0389%
Overall
0.00335%
54/1,614,186 alleles · ultra-rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 0.0573% | 1,745 |
| Admixed American | 0.005% | 20,010 |
| Remaining individualsnot grpmax-eligible | 0.0048% | 20,836 |
| South Asian | 0.0022% | 45,538 |
| European (non-Finnish) | 0.000254% | 393,348 |
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.Ala653=
- Coding
- c.1959C>T
- MANE Select
- NM_001291303
- dbSNP
- rs191491571
- Type
- single nucleotide variant
- Location
- chr4:125318370 (GRCh38)
- Gene constraint
- LOEUF 0.317 · pLI 1.00 (gnomAD)
- Residue 653
- the cadherin 6 domain
Similar variants
- FAT4 p.Ala653Val 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-ala653 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown