FAT2 p.Pro4259=
c.12777C>G · rs375536782 · VCV2083340
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.0974%, afr)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| REVEL | 0.4 | indeterminate |
|---|---|---|
| Splicing | ||
| SpliceAI | <0.2 | no splice effect predicted · four deltas, not one · how we know |
| Constraint at this position | ||
| Conservation | phyloP 1.7 | GERP 0.5, phastCons 1 |
| Overall | ||
| CADD | 6.59 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0974%
African / African-American · 73/74,980 alleles
Filtering AF
0.0794%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0728%
Overall
0.0049%
79/1,612,906 alleles · ultra-rare
exomes 38/1,460,594 · genomes 41/152,312 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 0.0974% | 1,027 |
| Remaining individualsnot grpmax-eligible | 0.00641% | 15,607 |
| Admixed American | 0.00336% | 29,786 |
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.Pro4259=
- Coding
- c.12777C>G
- MANE Select
- NM_001447
- dbSNP
- rs375536782
- Type
- single nucleotide variant
- Location
- chr5:151505838 (GRCh38)
- Gene constraint
- LOEUF 0.554 · pLI <0.01 (gnomAD)
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-pro4259 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown