F2 p.Ser331=
c.993G>A · rs375641046 · VCV1768675
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
very rare (popmax 0.00678%, nfe)
Conditions
2
Inborn genetic diseases
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 -15 | GERP -3 |
| Overall | ||
| CADD | 0.083 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00678%
European (non-Finnish) · 80/1,179,984 alleles
Filtering AF
0.00554%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00514%
Overall
0.00576%
93/1,613,974 alleles · very rare
exomes 79/1,461,758 · genomes 14/152,216 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| European (non-Finnish)grpmax | 0.00678% | 14,750 |
| Remaining individualsnot grpmax-eligible | 0.0048% | 20,826 |
| Finnishnot grpmax-eligible | 0.00469% | 21,336 |
| East Asian | 0.00446% | 22,446 |
| African / African-American | 0.004% | 24,981 |
| South Asian | 0.0022% | 45,533 |
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
- F2
- Protein
- p.Ser331=
- Coding
- c.993G>A
- MANE Select
- NM_000506
- dbSNP
- rs375641046
- Type
- single nucleotide variant
- Location
- chr11:46726616 (GRCh38)
- Gene constraint
- LOEUF 0.552 · pLI 0.15 (gnomAD)
- Structure
- AlphaFold pLDDT 84.37 · 480 PDB
- Residue 331
- an α-helix
Similar variants
- F2 p.Ser331Leu Conflicting classifications of pathogenicity ★ ⚠ same residue
- F2 p.Arg461Trp Pathogenic/Likely pathogenic ★★ same condition
- F2 p.Arg500Gln Pathogenic ★★ ⚠ same condition
- F2 p.Arg581Cys Pathogenic/Likely pathogenic ★★ same condition
- F2 p.Arg596Gln Pathogenic ★★ ⚠ same condition
- F2 p.Gln387Ter Pathogenic/Likely pathogenic ★★ same condition
- F2 c.559+5G>A Uncertain significance ★★ same condition
- F2 p.Ala17Ser Uncertain significance ★★ ⚠ same condition
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/f2-p-ser331 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown