FAT2 p.Pro4146=
c.12438C>G · rs368309685 · VCV2975416
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.0822%, mid)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| REVEL | 0.061 | moderately benign-leaning |
|---|---|---|
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
| Constraint at this position | ||
| Conservation | phyloP 0.46 | GERP -0.84, phastCons 0.99 |
| Overall | ||
| CADD | 0.509 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0822%
Middle Eastern · 5/6,082 alleles
Filtering AF
0.0323%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.021%
Overall
0.00186%
30/1,613,646 alleles · ultra-rare
exomes 22/1,461,466 · genomes 8/152,180 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Middle Easterngrpmax | 0.0822% | 1,216 |
| South Asian | 0.00769% | 13,006 |
| Admixed American | 0.00667% | 14,999 |
| Remaining individualsnot grpmax-eligible | 0.0048% | 20,823 |
| European (non-Finnish) | 0.000932% | 107,249 |
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.Pro4146=
- Coding
- c.12438C>G
- MANE Select
- NM_001447
- dbSNP
- rs368309685
- Type
- single nucleotide variant
- Location
- chr5:151507233 (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-pro4146 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown