FAT2 p.Ser506=
c.1518T>C · rs1240183407 · VCV2655966
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
very rare (popmax 0.00483%, nfe)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Splicing | ||
| SpliceAI | <0.2 | no splice effect predicted · four deltas, not one · how we know |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP -0.12 | GERP -4.4, phastCons 0.008 |
| Overall | ||
| CADD | 4.127 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00483%
European (non-Finnish) · 57/1,180,050 alleles
Filtering AF
0.00377%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00345%
Overall
0.00372%
60/1,614,118 alleles · very rare
exomes 59/1,461,878 · genomes 1/152,240 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| European (non-Finnish)grpmax | 0.00483% | 20,703 |
| Remaining individualsnot grpmax-eligible | 0.0032% | 31,244 |
| South Asian | 0.0011% | 91,090 |
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
- FAT2
- Protein
- p.Ser506=
- Coding
- c.1518T>C
- MANE Select
- NM_001447
- dbSNP
- rs1240183407
- Type
- single nucleotide variant
- Location
- chr5:151567414 (GRCh38)
- Gene constraint
- LOEUF 0.554 · pLI <0.01 (gnomAD)
- Residue 506
- the cadherin 4 domain
Similar variants
- FAT2 p.Ala1009Val Uncertain significance ★★ ⚠ same type
- FAT2 p.Ala1078Thr Uncertain significance ★★ ⚠ same type
- FAT2 p.Ala1079Asp Uncertain significance ★★ ⚠ same type
- FAT2 p.Ala1975Glu Uncertain significance ★★ same type
- FAT2 p.Ala2491Glu Uncertain significance ★★ same type
- FAT2 p.Ala249Val Uncertain significance ★★ ⚠ same type
- FAT2 p.Ala2587Val Uncertain significance ★★ same type
- FAT2 p.Ala2618Thr 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/fat2-p-ser506 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown