Benign
Single submitter
Classification
Benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
low-frequency (popmax 2.67%, sas)
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 4.6 | GERP 0.85, phastCons 1 |
| Overall | ||
| CADD | 9.28 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
2.67%
South Asian · 2,430/91,084 alleles
Filtering AF
2.58%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 2.54%
Overall
0.161%
2,597/1,611,854 alleles · low-frequency
exomes 2,455/1,459,540 · genomes 142/152,314 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| South Asiangrpmax | 2.67% | 37 |
| Remaining individualsnot grpmax-eligible | 0.179% | 558 |
| Middle Eastern | 0.115% | 866 |
| African / African-American | 0.0107% | 9,381 |
| European (non-Finnish) | 0.00331% | 30,257 |
| East Asian | 0.00223% | 44,888 |
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
- FOS
- Protein
- p.Val327=
- Coding
- c.981G>A
- MANE Select
- NM_005252
- dbSNP
- rs4645857
- Type
- single nucleotide variant
- Location
- chr14:75281262 (GRCh38)
- Gene constraint
- LOEUF 0.581 · pLI 0.87 (gnomAD)
- Structure
- AlphaFold pLDDT 58.48 · 3 PDB
Similar variants
- FOS p.Val327Leu Uncertain significance ★ ⚠ same residue
- FOS p.Lys176Asn Benign/Likely benign ★★ ⚠ same type
- FOS p.Pro233= Likely benign ★★ same type
- FOS p.Pro233Ala Likely benign ★★ same type
- FOS p.Thr63= Benign ★★ same type
- FOS p.Arg155Cys Likely pathogenic ★ same type
- FOS p.Ala103Val Uncertain significance ★ ⚠ same type
- FOS p.Ala184Asp 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/fos-p-val327 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown