FAT2 p.Leu331=
c.993C>T · rs77966518 · VCV2043599
Benign/Likely benign
Multiple submitters
Classification
Benign/Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
low-frequency (popmax 1.76%, 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 2.6 | GERP -1.1, phastCons 1 |
| Overall | ||
| CADD | 6.166 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
1.76%
African / African-American · 1,318/75,048 alleles
Filtering AF
1.68%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 1.65%
Overall
0.0895%
1,445/1,614,206 alleles · low-frequency
exomes 738/1,461,870 · genomes 707/152,336 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 1.76% | 57 |
| Remaining individualsnot grpmax-eligible | 0.0976% | 1,025 |
| Admixed American | 0.0766% | 1,305 |
| Middle Eastern | 0.066% | 1,516 |
| South Asian | 0.00549% | 18,216 |
| European (non-Finnish) | 0.000932% | 107,277 |
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.Leu331=
- Coding
- c.993C>T
- MANE Select
- NM_001447
- dbSNP
- rs77966518
- Type
- single nucleotide variant
- Location
- chr5:151567939 (GRCh38)
- Gene constraint
- LOEUF 0.554 · pLI <0.01 (gnomAD)
Similar variants
- FAT2 p.Leu331Phe Uncertain significance ★★ same residue
- 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
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-leu331 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown