FAT4 p.Ala277=
c.831G>A · rs142490028 · VCV516667
Benign
Multiple submitters
Classification
Benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 3 submitters
gnomAD v4.1
Common
common (popmax 6.9%, eas) — too common for a highly-penetrant pathogenic allele
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 -2.2 | GERP -4.5 |
| Overall | ||
| CADD | 8.728 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
6.9%
East Asian · 3,065/44,408 alleles
Filtering AF
6.7%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 6.63%
Overall
0.624%
9,848/1,578,720 alleles · common
exomes 9,111/1,426,392 · genomes 737/152,328 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| East Asiangrpmax | 6.9% | 14 |
| South Asian | 6.83% | 15 |
| Remaining individualsnot grpmax-eligible | 0.795% | 126 |
| Middle Eastern | 0.339% | 295 |
| Admixed American | 0.0904% | 1,107 |
| African / African-American | 0.0835% | 1,198 |
| European (non-Finnish) | 0.0242% | 4,128 |
| Finnishnot grpmax-eligible | 0.00809% | 12,359 |
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.Ala277=
- Coding
- c.831G>A
- MANE Select
- NM_001291303
- dbSNP
- rs142490028
- Type
- single nucleotide variant
- Location
- chr4:125317242 (GRCh38)
- Gene constraint
- LOEUF 0.317 · pLI 1.00 (gnomAD)
- Residue 277
- the cadherin 3 domain
Similar variants
- FAT4 p.Ala277Thr 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-ala277 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown