F8 p.Gly89Ser
c.265G>A · VCV3766866
Pathogenic
Single submitter
Classification
Pathogenic
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
AlphaMissense
likely pathogenic
0.6455 · ACMG-weighted
gnomAD v4.1
Absent
absent from gnomAD v4.1
Missense predictors
3/3 damaging
AlphaMissense, REVEL, SaProt
Computational evidence
| Protein change | ||
| AlphaMissense | 0.6455 | likely pathogenic ✓ concordant with ClinVar |
|---|---|---|
| REVEL | 0.894 | moderately pathogenic-leaning |
| SaProt | LLR -12.09 | damaging |
| ⇒ AlphaMissense, REVEL and SaProt all call this damaging. | ||
| Splicing | ||
| SpliceAI | Δ0.68 | donor loss · deltas |
| Pangolin | Δ0.59 | loss · gain 0.05 · agrees with SpliceAI · independent |
| Constraint at this position | ||
| Conservation | phyloP 7.5 | GERP 1.4, phastCons 1 |
| Regional constraint | o/e 0.56 | unconstrained · MANE · 53 kb · p 1.5e-11 · regional, not allelic |
| Overall | ||
| CADD | 33.0 | PHRED · no single calibrated threshold — expert panels disagree |
AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.
Population frequency
gnomAD v4.1 · exomes + genomes
Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.
Variant & gene context
- Gene
- F8
- Protein
- p.Gly89Ser
- Coding
- c.265G>A
- MANE Select
- NM_000132
- Type
- single nucleotide variant
- Location
- chrX:154999479 (GRCh38)
- Structure
- AlphaFold pLDDT 61.20 · 29 PDB
- Residue 89
- a turn; the f5/8 type a 1 domain; the plastocyanin-like 1 domain; a UniProt-annotated variant site (in hema; severe); a UniProt-annotated variant site (in hema; mild)
Similar variants
- F8 p.Gly89Asp Pathogenic same residue
- F8 c.6429+2T>A Pathogenic ★★★ same type
- F8 p.Ala111Thr Likely pathogenic ★★★ same type
- F8 p.Ala2220Pro Pathogenic ★★★ same type
- F8 p.Ala415Asp Likely pathogenic ★★★ same type
- F8 p.Ala415Val Pathogenic ★★★ ⚠ same type
- F8 p.Arg1768His Pathogenic ★★★ ⚠ same type
- F8 p.Arg1800His 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/f8-p-gly89ser (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown