FAT1 p.Val976=
c.2928G>C · rs114279527 · VCV1261998
Benign/Likely benign
Multiple submitters
Classification
Benign/Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 5 submitters
gnomAD v4.1
Common
common (popmax 5.48%, mid) — 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 | <0.2 | no splice effect predicted · four deltas, not one · how we know |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP 0.7 | GERP -2, phastCons 1 |
| Overall | ||
| CADD | 0.691 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
5.48%
Middle Eastern · 332/6,062 alleles
Filtering AF
5.18%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 5.13%
Overall
3.79%
61,140/1,613,954 alleles · common
exomes 56,711/1,461,694 · genomes 4,429/152,260 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Middle Easterngrpmax | 5.48% | 18 |
| South Asian | 5.3% | 19 |
| Ashkenazi Jewishnot grpmax-eligible | 4.36% | 23 |
| European (non-Finnish) | 4.05% | 25 |
| Remaining individualsnot grpmax-eligible | 3.85% | 26 |
| Finnishnot grpmax-eligible | 3.73% | 27 |
| Admixed American | 2.63% | 38 |
| Amishnot grpmax-eligible | 1.64% | 61 |
| African / African-American | 0.702% | 142 |
| East Asian | 0.0201% | 4,987 |
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
- FAT1
- Protein
- p.Val976=
- Coding
- c.2928G>C
- MANE Select
- NM_005245
- dbSNP
- rs114279527
- Type
- single nucleotide variant
- Location
- chr4:186706900 (GRCh38)
- Gene constraint
- LOEUF 0.571 · pLI <0.01 (gnomAD)
- Residue 976
- the cadherin 8 domain
Similar variants
- FAT1 p.Ala1663Thr Uncertain significance ★★ same type
- FAT1 p.Ala1762Val Uncertain significance ★★ ⚠ same type
- FAT1 p.Ala1862Ser Uncertain significance ★★ ⚠ same type
- FAT1 p.Ala2046Thr Uncertain significance ★★ ⚠ same type
- FAT1 p.Ala2456Thr Uncertain significance ★★ ⚠ same type
- FAT1 p.Ala2502Asp Uncertain significance ★★ ⚠ same type
- FAT1 p.Ala3007Val Uncertain significance ★★ same type
- FAT1 p.Ala3437Thr 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/fat1-p-val976 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown