F7 p.Thr75=
c.225G>C · VCV3340422
Likely pathogenic
Single submitter
Classification
Likely pathogenic
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 8.68e-05%, nfe)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation/SpliceAI carries the signal. | ||
| Splicing | ||
| SpliceAI | Δ0.60 | donor loss · deltas |
|---|---|---|
| Pangolin | Δ0.62 | loss · gain 0.01 · agrees with SpliceAI · independent |
| Constraint at this position | ||
| Conservation | phyloP -0.2 | GERP -3.8, phastCons 0.083 |
| Overall | ||
| CADD | 16.05 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
8.68e-05%
European (non-Finnish) · 1/1,151,836 alleles
Overall
7.11e-05%
1/1,405,992 alleles · very rare
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
- F7
- Protein
- p.Thr75=
- Coding
- c.225G>C
- MANE Select
- NM_019616
- Type
- single nucleotide variant
- Location
- chr13:113110850 (GRCh38)
- Gene constraint
- LOEUF 1.113 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
- Structure
- AlphaFold pLDDT 82.64 · 114 PDB
- Residue 75
- an α-helix; the gla domain
Similar variants
- F7 p.Thr75Met Uncertain significance ★★ ⚠ same residue
- F7 c.225+1G>C Pathogenic ★★ same type
- F7 c.364+1G>A Pathogenic/Likely pathogenic ★★ same type
- F7 c.365-2A>G Likely pathogenic ★★ same type
- F7 c.505+78G>A Pathogenic/Likely pathogenic ★★ same type
- F7 c.615+1G>T Pathogenic/Likely pathogenic ★★ same type
- F7 c.64+5G>A Pathogenic/Likely pathogenic ★★ same type
- F7 c.739+1G>A Pathogenic/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/f7-p-thr75 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown