F13A1 p.Pro565=
c.1695G>A · rs372651461 · VCV1343429
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
ultra-rare (popmax 0.0583%, amr)
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 1.1 | GERP -4.3, phastCons 1 |
| Overall | ||
| CADD | 9.275 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0583%
Admixed American · 35/59,998 alleles
Filtering AF
0.0431%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0378%
Overall
0.00675%
109/1,614,014 alleles · ultra-rare
exomes 83/1,461,880 · genomes 26/152,134 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Admixed Americangrpmax | 0.0583% | 1,714 |
| Middle Eastern | 0.0329% | 3,042 |
| Remaining individualsnot grpmax-eligible | 0.0096% | 10,415 |
| European (non-Finnish) | 0.00542% | 18,438 |
| African / African-American | 0.00133% | 74,920 |
| South Asian | 0.0011% | 91,078 |
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
- F13A1
- Protein
- p.Pro565=
- Coding
- c.1695G>A
- MANE Select
- NM_000129
- dbSNP
- rs372651461
- Type
- single nucleotide variant
- Location
- chr6:6174632 (GRCh38)
- Gene constraint
- LOEUF 0.734 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 91.15 · 15 PDB
- Residue 565
- a β-strand; a UniProt-annotated variant site (in allele f13a*1a, allele f13a*2a and allele f13*(2)a)
Similar variants
- F13A1 p.Pro565Leu Conflicting classifications of pathogenicity ★ ⚠ same residue
- F13A1 c.691-1G>A Pathogenic/Likely pathogenic ★★ same type
- F13A1 p.Arg327Gln Pathogenic/Likely pathogenic ★★ same type
- F13A1 p.Arg409Gln Likely pathogenic ★★ ⚠ same type
- F13A1 p.Arg662Ter Pathogenic ★★ same type
- F13A1 p.Arg682His Pathogenic ★★ ⚠ same type
- F13A1 p.Arg78Cys Pathogenic/Likely pathogenic ★★ same type
- F13A1 p.Gly274Arg Likely pathogenic ★★ 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/f13a1-p-pro565 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown