Is F8 p.Ser1806Phe (c.5417C>T) pathogenic?

F8 p.Ser1806Phe (c.5417C>T) is classified Likely pathogenic in F8 (ClinVar, Single submitter, 1 submitter; last evaluated 2017-10-18). AlphaMissense: likely pathogenic (0.8034); Absent from gnomAD v4.1.

How common is F8 p.Ser1806Phe (c.5417C>T) in the general population?

F8 p.Ser1806Phe (c.5417C>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about F8 p.Ser1806Phe (c.5417C>T)?

AlphaMissense predicts likely pathogenic (score 0.8034) — an in-silico prediction, not a clinical call.

F8 p.Ser1806Phe

c.5417C>T · rs1569559523 · VCV618634

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.8034 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.8034	likely pathogenic ✓ concordant with ClinVar · top 9% in F8
REVEL	0.807	moderately pathogenic-leaning
SaProt	LLR -9.77	tolerated
⇒ AlphaMissense and REVEL call this damaging; SaProt does not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 1.6, phastCons 1
Regional constraint	o/e 0.65	unconstrained · MANE · 91 kb · p 1.5e-14 · regional, not allelic
Overall
CADD	24.0	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.Ser1806Phe
Coding: c.5417C>T
MANE Select: NM_000132
dbSNP: rs1569559523
Type: single nucleotide variant
Location: chrX:154904980 (GRCh38)
Structure: AlphaFold pLDDT 61.20 · 29 PDB
Residue 1806: the f5/8 type a 3 domain; the plastocyanin-like 5 domain

Full F8 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

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
F8 p.Arg2016Trp 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-ser1806phe (accessed [today's date]).

Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown